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

Yun Chai; Zhi-Long Wan; Hui-Yuan Guo; Ming-Liang Liu

doi:10.1107/S1600536809000634

. 2009 Jan 10;65(Pt 2):o282. doi: 10.1107/S1600536809000634

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

Yun Chai ^a, Zhi-Long Wan ^a, Hui-Yuan Guo ^a, Ming-Liang Liu ^a,^*

PMCID: PMC2968237 PMID: 21581895

Abstract

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.

Related literature

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

Crystal data

C₁₃H₂₃N₃O₄
M _r = 285.34
Triclinic,
a = 7.3750 (14) Å
b = 10.0132 (16) Å
c = 11.3383 (18) Å
α = 79.5710 (10)°
β = 73.0340 (10)°
γ = 84.973 (2)°
V = 787.1 (2) Å³
Z = 2
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 298 (2) K
0.50 × 0.45 × 0.44 mm

Data collection

Bruker SMART APEX CCD diffractometer
Absorption correction: multi-scan (SADABS; Sheldrick, 1996 ▶) T _min = 0.946, T _max = 0.963
4100 measured reflections
2727 independent reflections
1535 reflections with I > 2σ(I)
R _int = 0.041

Refinement

R[F ² > 2σ(F ²)] = 0.056
wR(F ²) = 0.176
S = 1.04
2727 reflections
187 parameters
H-atom parameters constrained
Δρ_max = 0.22 e Å⁻³
Δρ_min = −0.18 e Å⁻³

Data collection: SMART (Bruker, 1998 ▶); cell refinement: SAINT (Bruker, 1999 ▶); data reduction: SAINT; 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.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809000634/is2378sup1.cif

e-65-0o282-sup1.cif^{(19.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809000634/is2378Isup2.hkl

e-65-0o282-Isup2.hkl^{(133.9KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2B⋯O2	0.86	2.25	3.026 (3)	150
N2—H2A⋯O3ⁱ	0.86	2.06	2.913 (3)	173

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Symmetry code: (i) Inline graphic .

Acknowledgments

This work was supported by the IMB Research Foundation.

supplementary crystallographic information

Comment

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)

Experimental

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)⁺.