Diisopropylethylamine → (S)-4-(4-Fluorophenyl)-5,5-dimethyl-3-(4-((3-nitropyridin-4-yl)amino)cyclohexyl)oxazolidin-2-one

HRID 525367Notes

Reaction equation

[NH2:1][CH:2]1[CH2:7][CH2:6][CH:5]([N:8]2[C@@H:12]([C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[C:11]([CH3:21])([CH3:20])[O:10][C:9]2=[O:22])[CH2:4][CH2:3]1.CCN(C(C)C)C(C)C.Cl[C:33]1[CH:38]=[CH:37][N:36]=[CH:35][C:34]=1[N+:39]([O-:41])=[O:40]>C(#N)C>[F:19][C:16]1[CH:15]=[CH:14][C:13]([C@H:12]2[C:11]([CH3:20])([CH3:21])[O:10][C:9](=[O:22])[N:8]2[CH:5]2[CH2:4][CH2:3][CH:2]([NH:1][C:33]3[CH:38]=[CH:37][N:36]=[CH:35][C:34]=3[N+:39]([O-:41])=[O:40])[CH2:7][CH2:6]2)=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To a vial charged with (S)-3-(4-aminocyclohexyl)-4-(4-fluorophenyl)-5,5-dimethyloxazolidin-2-one (0.320 g, 1.044 mmol) were added ACN (3.48 mL), DIEA (0.365 mL, 2.089 mmol) and 4-chloro-3-nitropyridine (commercially available from Sigma-Aldrich, Milwaukee, Wis.) (0.166 g, 1.044 mmol) respectively. The vial was sealed and heated at 80° C. for 2 hours leading to ˜90% conversion to the desired product with starting amine present. Additional chloropyridine (0.2 eq) and DIEA (0.2 eq) were added, and the mixture was heated at 80° C. for an additional 15 hours. The dark mixture was dried under reduced pressure and purified with a 25 g HP spherical silica column ramping DCM:MeOH (90:10) in DCM from 0-50%, then isocratic at 50% (detection at 215 nm) leading to isolation of (S)-4-(4-fluorophenyl)-5,5-dimethyl-3-(4-((3-nitropyridin-4-yl)amino)cyclohexyl)oxazolidin-2-one (0.286 g, 0.668 mmol, 63.9% yield) as an orange/brown oil and as a mixture of cis/trans isomers. m/z (ESI) 429.0 (M+H)+.

Workup

customThe vial was sealed

Sources & evidence

ORD record: ord-cec4f4a5426a4028a97a2fa219aa2239
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09340549B2

Reaction notes

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