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Acta Cryst. (2009). E65, o282    [ doi:10.1107/S1600536809000634 ]

tert-Butyl 3-carbamoyl-4-methoxyimino-3-methylpiperidine-1-carboxylate

Y. Chai, Z.-L. Wan, H.-Y. Guo and M.-L. Liu

Abstract top

In the title compound, C13H23N3O4, the piperidine ring adopts a chair conformation. An intramolecular N-H...O hydrogen bond is observed between the carbamoyl and carboxylate groups. In the crystal structure, molecules form inversion dimers linked by pairs of N-H...O hydrogen bonds.

Comment top

Quinolone antibacterial agents have emerged as one of the dominant classes of chemotherapeutic drugs for the treatment of various bacterial infections in both community and hospital settings (Ray et al., 2005; Ball et al., 1998). In general, 5- and 6 -membered nitrogen heterocycles including piperazinyl, pyrrolidinyl and piperidinyl type side chains have been proven to be the optimal substituents (Anderson & Osheroff, 2001; Choi et al., 2004). Recently, as part of an ongoing program to find potent new quinolones displaying strong Gram-positive activity, we have focused our attention on introducing new functional groups to the piperidine ring (Wang, Guo & Wang, 2008; Wang, Liu & Cao, 2008). We report here the crystal structure of the title compound, which is a key intermediate of 3-amino-4-methoxyimino-3-methylpiperidine, a novel C-7 substituent of the quinolones.

In the molecule of the title compound (Fig. 1), the N1—C1 [1.352 (3) Å] and N2—C7 [1.320 (3) Å] bond lengths are significantly shorter than the normal C—N single bond (1.47 Å), indicating some conjugation with the C1═O2 and C7═O3 carbonyl groups, respectively. The six-membered piperidine ring adopts a chair conformation. In the crystal structure, the molecules have an intramolecular N—H···O and an intermolecular N—H···O hydrogen bond (Table 1 & Fig. 2)

Related literature top

For the synthesis and properties of quinolone derivatives, see: Anderson & Osheroff (2001); Ball et al. (1998); Choi et al. (2004); Ray et al. (2005); Wang, Guo & Wang (2008); Wang, Liu & Cao (2008).

Experimental top

The title compound was prepared from methyl N-tert-butoxycarbonyl-4- methoxyimino-3-methylpiperidine-3-carboxylate. To a stirring solution of methyl N-tert-butoxycarbonyl-4-methoxyimino-3-methylpiperidine-3-carboxylate (17.00 g, 56.6 mmol) in methanol (100 ml) was added dropwise a solution of sodium hydroxide (4.53 g, 113.2 mmol) dissolved in distilled water (20 ml) at room temperature. The reaction mixture was heated to 50 °C and stirred for 2 h at the same temperature. After removal of the methanol under reduced pressure, the reaction mixture was diluted with distilled water (30 ml), adjusted to pH 6.0–6.5 with acetic acid. The solid collected by suction was dissolved in methylene chloride (150 ml), and to this solution was added triethylamine (8.8 ml, 63.6 mmol). The reaction mixture was cooled to -14 °C, using an ice-salt bath, isobutyl chloroformate (9.0 ml, 69.2 mmol) was added and stirred for 0.5 h at the same temperature, pumped ammonia gas cautiously at 0–5 °C for 0.5 h, washed with 1 N HCl and saturated brine, respectively, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting yellow residue was recrystallized from ethyl acetate to give the title compound (13.50 g, 83.6%; m.p. 126–127 °C) as a white solid. Single crystals suitable for X-ray analysis were obtained by slow evaporation of an ethyl acetate solution. 1H NMR (CDCl3, δ): 1.37 (3H, s, CH3), 1.47 (9H, s, CH3), 2.14–3.86 (4H, m, C5, C6), 3.89 (3H, s, OCH3), 4.35–4.37 (2H, m,C2), 5.37 (1H, br, CONH), 6.19 (1H, br, CONH). MS (ESI, m/z): 286 (M+H)+.

Refinement top

All H atoms were placed at calculated positions, with C—H = 0.96–0.97Å and N—H= 0.86 Å, and were included in the final cycles of refinement using a riding model, with Uiso(H) = 1.2Ueq(C, N) or 1.5Ueq(methyl C), allowing for free rotation of the methyl groups.

Computing details top

Data collection: SMART (Bruker, 1998); cell refinement: SAINT (Bruker, 1999); data reduction: SAINT (Bruker, 1999); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. The molecular structure of (I), showing 40% probability displacement ellipsoids and the atom-numbering scheme.
[Figure 2] Fig. 2. The crystal packing of the title compound.
tert-Butyl 3-carbamoyl-4-methoxyimino-3-methylpiperidine-1-carboxylate top
Crystal data top
C13H23N3O4Z = 2
Mr = 285.34F(000) = 308
Triclinic, P1Dx = 1.204 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.3750 (14) ÅCell parameters from 1147 reflections
b = 10.0132 (16) Åθ = 2.6–23.6°
c = 11.3383 (18) ŵ = 0.09 mm−1
α = 79.571 (1)°T = 298 K
β = 73.034 (1)°Block, colorless
γ = 84.973 (2)°0.50 × 0.45 × 0.44 mm
V = 787.1 (2) Å3
Data collection top
Bruker SMART APEX CCD
diffractometer		2727 independent reflections
Radiation source: fine-focus sealed tube1535 reflections with I > 2σ(I)
graphiteRint = 0.041
φ and ω scansθmax = 25.0°, θmin = 1.9°
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)		h = −7→8
Tmin = 0.946, Tmax = 0.963k = −11→10
4100 measured reflectionsl = −12→13
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.056H-atom parameters constrained
wR(F2) = 0.176 w = 1/[σ2(Fo2) + (0.0793P)2]
where P = (Fo2 + 2Fc2)/3
S = 1.04(Δ/σ)max = 0.001
2727 reflectionsΔρmax = 0.22 e Å−3
187 parametersΔρmin = −0.18 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.052 (9)
Crystal data top
C13H23N3O4γ = 84.973 (2)°
Mr = 285.34V = 787.1 (2) Å3
Triclinic, P1Z = 2
a = 7.3750 (14) ÅMo Kα radiation
b = 10.0132 (16) ŵ = 0.09 mm−1
c = 11.3383 (18) ÅT = 298 K
α = 79.571 (1)°0.50 × 0.45 × 0.44 mm
β = 73.034 (1)°
Data collection top
Bruker SMART APEX CCD
diffractometer		2727 independent reflections
Absorption correction: multi-scan
(SADABS; Sheldrick, 1996)		1535 reflections with I > 2σ(I)
Tmin = 0.946, Tmax = 0.963Rint = 0.041
4100 measured reflectionsθmax = 25.0°
Refinement top
R[F2 > 2σ(F2)] = 0.056H-atom parameters constrained
wR(F2) = 0.176Δρmax = 0.22 e Å−3
S = 1.04Δρmin = −0.18 e Å−3
2727 reflectionsAbsolute structure: ?
187 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
N10.3951 (3)0.3430 (2)0.4995 (2)0.0486 (6)
N20.0625 (3)0.1810 (2)0.4744 (2)0.0647 (8)
H2A0.03020.12510.43550.078*
H2B0.09180.26230.43740.078*
N30.1916 (3)0.1524 (2)0.8514 (2)0.0485 (6)
O10.6155 (3)0.3495 (2)0.31633 (18)0.0636 (6)
O20.3110 (3)0.4119 (2)0.32090 (19)0.0649 (6)
O30.0266 (4)0.0264 (2)0.6479 (2)0.0825 (8)
O40.3333 (3)0.0907 (2)0.90663 (17)0.0580 (6)
C10.4323 (4)0.3706 (3)0.3737 (3)0.0504 (7)
C20.2080 (4)0.3727 (3)0.5782 (3)0.0502 (7)
H2C0.12900.41490.52570.060*
H2D0.21800.43730.63010.060*
C30.1121 (4)0.2457 (3)0.6625 (2)0.0453 (7)
C40.2516 (4)0.1757 (3)0.7326 (2)0.0426 (7)
C50.4480 (4)0.1488 (3)0.6534 (3)0.0533 (8)
H5A0.44540.08020.60360.064*
H5B0.52890.11420.70670.064*
C60.5292 (4)0.2785 (3)0.5672 (3)0.0549 (8)
H6A0.55450.34090.61630.066*
H6B0.64800.25670.50820.066*
C70.0673 (4)0.1420 (3)0.5911 (3)0.0523 (7)
C8−0.0772 (4)0.2898 (3)0.7492 (3)0.0632 (9)
H8A−0.13960.21110.80170.095*
H8B−0.15650.33660.69990.095*
H8C−0.05380.34940.80030.095*
C90.2502 (5)0.0608 (4)1.0379 (3)0.0750 (10)
H9A0.22370.14381.07190.112*
H9B0.33640.00361.07560.112*
H9C0.13420.01481.05480.112*
C100.6835 (5)0.3554 (3)0.1795 (3)0.0698 (10)
C110.5789 (7)0.2537 (4)0.1411 (4)0.1179 (17)
H11A0.59460.16480.18650.177*
H11B0.62970.25250.05300.177*
H11C0.44640.27960.15940.177*
C120.6609 (5)0.4976 (3)0.1139 (3)0.0817 (11)
H12A0.52860.52350.13070.123*
H12B0.71580.50150.02550.123*
H12C0.72410.55880.14360.123*
C130.8911 (6)0.3152 (5)0.1616 (4)0.1190 (17)
H13A0.95030.38010.18980.179*
H13B0.95210.31320.07460.179*
H13C0.90250.22670.20900.179*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0479 (14)0.0503 (14)0.0474 (14)−0.0055 (11)−0.0176 (11)0.0010 (11)
N20.088 (2)0.0558 (15)0.0618 (17)−0.0246 (13)−0.0409 (15)0.0035 (12)
N30.0467 (14)0.0515 (14)0.0507 (15)0.0004 (10)−0.0223 (12)−0.0041 (11)
O10.0670 (15)0.0675 (14)0.0497 (13)−0.0009 (11)−0.0118 (11)−0.0012 (10)
O20.0748 (15)0.0634 (13)0.0592 (13)−0.0091 (11)−0.0332 (12)0.0098 (10)
O30.130 (2)0.0610 (15)0.0685 (15)−0.0418 (14)−0.0493 (15)0.0113 (11)
O40.0497 (12)0.0750 (14)0.0472 (12)0.0076 (10)−0.0202 (9)0.0013 (10)
C10.060 (2)0.0407 (16)0.0516 (18)−0.0073 (14)−0.0207 (16)0.0003 (13)
C20.0539 (18)0.0430 (16)0.0570 (18)0.0003 (13)−0.0233 (15)−0.0048 (13)
C30.0460 (16)0.0454 (15)0.0483 (16)−0.0040 (12)−0.0214 (13)−0.0028 (12)
C40.0469 (16)0.0385 (14)0.0454 (17)−0.0041 (12)−0.0180 (13)−0.0050 (12)
C50.0521 (17)0.0562 (18)0.0506 (17)0.0067 (14)−0.0195 (14)−0.0023 (14)
C60.0487 (17)0.0651 (19)0.0513 (18)−0.0047 (14)−0.0197 (14)−0.0001 (14)
C70.0566 (18)0.0502 (18)0.0550 (19)−0.0094 (14)−0.0271 (15)0.0013 (14)
C80.0476 (18)0.072 (2)0.066 (2)0.0032 (15)−0.0190 (15)−0.0008 (16)
C90.067 (2)0.106 (3)0.0469 (19)0.0100 (19)−0.0218 (17)0.0019 (18)
C100.091 (3)0.061 (2)0.0489 (19)−0.0032 (18)−0.0078 (18)−0.0056 (15)
C110.183 (5)0.084 (3)0.081 (3)−0.036 (3)−0.008 (3)−0.031 (2)
C120.109 (3)0.071 (2)0.059 (2)−0.018 (2)−0.020 (2)0.0060 (17)
C130.123 (4)0.124 (4)0.072 (3)0.029 (3)0.012 (3)0.001 (2)
Geometric parameters (Å, °) top
N1—C11.352 (3)C5—H5B0.9700
N1—C21.447 (3)C6—H6A0.9700
N1—C61.461 (3)C6—H6B0.9700
N2—C71.320 (3)C8—H8A0.9600
N2—H2A0.8600C8—H8B0.9600
N2—H2B0.8600C8—H8C0.9600
N3—C41.274 (3)C9—H9A0.9600
N3—O41.412 (3)C9—H9B0.9600
O1—C11.334 (3)C9—H9C0.9600
O1—C101.477 (4)C10—C121.502 (4)
O2—C11.220 (3)C10—C131.512 (5)
O3—C71.234 (3)C10—C111.522 (5)
O4—C91.421 (3)C11—H11A0.9600
C2—C31.534 (3)C11—H11B0.9600
C2—H2C0.9700C11—H11C0.9600
C2—H2D0.9700C12—H12A0.9600
C3—C41.526 (3)C12—H12B0.9600
C3—C81.536 (4)C12—H12C0.9600
C3—C71.537 (4)C13—H13A0.9600
C4—C51.496 (4)C13—H13B0.9600
C5—C61.528 (4)C13—H13C0.9600
C5—H5A0.9700
C1—N1—C2120.1 (2)O3—C7—N2122.2 (3)
C1—N1—C6125.2 (2)O3—C7—C3118.3 (2)
C2—N1—C6114.7 (2)N2—C7—C3119.4 (2)
C7—N2—H2A120.0C3—C8—H8A109.5
C7—N2—H2B120.0C3—C8—H8B109.5
H2A—N2—H2B120.0H8A—C8—H8B109.5
C4—N3—O4112.3 (2)C3—C8—H8C109.5
C1—O1—C10121.1 (2)H8A—C8—H8C109.5
N3—O4—C9108.1 (2)H8B—C8—H8C109.5
O2—C1—O1125.0 (3)O4—C9—H9A109.5
O2—C1—N1123.0 (3)O4—C9—H9B109.5
O1—C1—N1112.0 (3)H9A—C9—H9B109.5
N1—C2—C3112.9 (2)O4—C9—H9C109.5
N1—C2—H2C109.0H9A—C9—H9C109.5
C3—C2—H2C109.0H9B—C9—H9C109.5
N1—C2—H2D109.0O1—C10—C12110.4 (3)
C3—C2—H2D109.0O1—C10—C13101.3 (3)
H2C—C2—H2D107.8C12—C10—C13110.6 (3)
C4—C3—C2106.7 (2)O1—C10—C11109.4 (3)
C4—C3—C8113.3 (2)C12—C10—C11112.3 (3)
C2—C3—C8108.6 (2)C13—C10—C11112.2 (3)
C4—C3—C7107.2 (2)C10—C11—H11A109.5
C2—C3—C7114.1 (2)C10—C11—H11B109.5
C8—C3—C7107.1 (2)H11A—C11—H11B109.5
N3—C4—C5127.1 (2)C10—C11—H11C109.5
N3—C4—C3117.0 (2)H11A—C11—H11C109.5
C5—C4—C3115.8 (2)H11B—C11—H11C109.5
C4—C5—C6110.8 (2)C10—C12—H12A109.5
C4—C5—H5A109.5C10—C12—H12B109.5
C6—C5—H5A109.5H12A—C12—H12B109.5
C4—C5—H5B109.5C10—C12—H12C109.5
C6—C5—H5B109.5H12A—C12—H12C109.5
H5A—C5—H5B108.1H12B—C12—H12C109.5
N1—C6—C5110.2 (2)C10—C13—H13A109.5
N1—C6—H6A109.6C10—C13—H13B109.5
C5—C6—H6A109.6H13A—C13—H13B109.5
N1—C6—H6B109.6C10—C13—H13C109.5
C5—C6—H6B109.6H13A—C13—H13C109.5
H6A—C6—H6B108.1H13B—C13—H13C109.5
C4—N3—O4—C9−176.3 (2)C2—C3—C4—C5−51.9 (3)
C10—O1—C1—O2−9.5 (4)C8—C3—C4—C5−171.3 (2)
C10—O1—C1—N1171.7 (2)C7—C3—C4—C570.7 (3)
C2—N1—C1—O2−5.1 (4)N3—C4—C5—C6−124.0 (3)
C6—N1—C1—O2172.4 (3)C3—C4—C5—C652.5 (3)
C2—N1—C1—O1173.8 (2)C1—N1—C6—C5−122.0 (3)
C6—N1—C1—O1−8.8 (4)C2—N1—C6—C555.6 (3)
C1—N1—C2—C3119.1 (3)C4—C5—C6—N1−50.8 (3)
C6—N1—C2—C3−58.6 (3)C4—C3—C7—O347.7 (3)
N1—C2—C3—C452.9 (3)C2—C3—C7—O3165.5 (3)
N1—C2—C3—C8175.4 (2)C8—C3—C7—O3−74.2 (3)
N1—C2—C3—C7−65.3 (3)C4—C3—C7—N2−136.3 (3)
O4—N3—C4—C5−2.0 (4)C2—C3—C7—N2−18.5 (4)
O4—N3—C4—C3−178.5 (2)C8—C3—C7—N2101.7 (3)
C2—C3—C4—N3124.9 (2)C1—O1—C10—C1266.9 (3)
C8—C3—C4—N35.5 (3)C1—O1—C10—C13−175.9 (3)
C7—C3—C4—N3−112.4 (3)C1—O1—C10—C11−57.2 (4)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H2B···O20.862.253.026 (3)150
N2—H2A···O3i0.862.062.913 (3)173
Symmetry codes: (i) −x, −y, −z+1.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N2—H2B···O20.862.253.026 (3)150
N2—H2A···O3i0.862.062.913 (3)173
Symmetry codes: (i) −x, −y, −z+1.
Acknowledgements top

This work was supported by the IMB Research Foundation.

references
References top

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