[(R)-5-difluoromethyl-5-(2-fluoro-5-nitro-phenyl)-5,6-dihydro-2H-[1,4]oxazin-3-yl]carbamic acid tert-butyl ester → [(R)-5-(5-Amino-2-fluoro-phenyl)-5-difluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

HRID 2196350Notes

Reaction equation

[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@@:12]([CH:24]([F:26])[F:25])([C:14]2[CH:19]=[C:18]([N+:20]([O-])=O)[CH:17]=[CH:16][C:15]=2[F:23])[N:13]=1)([CH3:4])([CH3:3])[CH3:2].[H][H]>CO.[OH-].[OH-].[Pd+2]>[C:1]([O:5][C:6](=[O:27])[NH:7][C:8]1[CH2:9][O:10][CH2:11][C@:12]([C:14]2[CH:19]=[C:18]([NH2:20])[CH:17]=[CH:16][C:15]=2[F:23])([CH:24]([F:26])[F:25])[N:13]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 20 °C

Procedure

To a suspension of [(R)-5-difluoromethyl-5-(2-fluoro-5-nitro-phenyl)-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (8 g, 19.23 mmol) in MeOH (56 mL) was added Pd(OH)2/C (20%, 50% water, 0.8 g). The atmosphere in the reactor was replaced by hydrogen (1 bar), then the reaction mixture was stirred at 20° C. for 5 h, filtered through Micro-crystals cellulose and concentrated. The crude product was recrystallized from MeOH and water to provide the title compound as a white solid: ESIMS: 360.1521; [(M+H)+]; 1H NMR (400 MHz, DMSO-d6): δ 9.99 (s, 1H), 6.83 (dd, 1H), 6.74 (m, 1H), 6.50 (m, 1H), 6.22 (t, 1H), 4.95 (s, 2H), 4.46 (dd, 2H), 4.03 (m, 1H), 3.84 (m, 1H), 1.42 (s, 9H).

Workup

filtrationfiltered through Micro-crystals cellulose
concentrationconcentrated
customThe crude product was recrystallized from MeOH and water

Sources & evidence

ORD record: ord-4f5e3fbe5d9e4379a8d7272ac7082b47
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08338413B1

Reaction notes

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