tert-Butyl ((2R,5R)-5-(2-fluoro-5-nitrophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-yl)carbamate → [(2R,5R)-5-(5-Amino-2-fluoro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

HRID 39240Notes

Reaction equation

HRID 39240 reaction equation
[C:1]([O:5][C:6](=[O:30])[NH:7][C:8]1[C@:9]([CH3:29])([C:25]([F:28])([F:27])[F:26])[O:10][CH2:11][C@:12]([C:15]2[CH:20]=[C:19]([N+:21]([O-])=O)[CH:18]=[CH:17][C:16]=2[F:24])([CH3:14])[N:13]=1)([CH3:4])([CH3:3])[CH3:2]>C(O)(C)C.C1COCC1.[Pd]>[C:1]([O:5][C:6](=[O:30])[NH:7][C:8]1[C@:9]([CH3:29])([C:25]([F:28])([F:27])[F:26])[O:10][CH2:11][C@:12]([C:15]2[CH:20]=[C:19]([NH2:21])[CH:18]=[CH:17][C:16]=2[F:24])([CH3:14])[N:13]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

4

Reactant 1

HCID 66666042tert-Butyl ((2R,5R)-5-(2-fluoro-5-nitrophenyl)-2,5-dimethyl-2-(trifluoromethyl)-5,6-dihydro-2H-1,4-oxazin-3-yl)carbamate

Product 1

HCID 66666212[(2R,5R)-5-(5-Amino-2-fluoro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 22597222Tetrahydrofuran 2-propanolSolvent

Procedure

A solution of [(2R,5R)-5-(2-fluoro-5-nitro-phenyl)-2,5-dimethyl-2-trifluoromethyl-5,6-dihydro-2H-[1,4]oxazin-3-yl]-carbamic acid tert-butyl ester (0.98 g, 2.25 mmol) in isopropanol-THF 2:1 (24 ml) was hydrogenated over 5% Pd—C for 4 h at 50° C. The catalyst was filtered off over Celite and the filtrate was concentrated to provide the title compound after crystallization from TBME-hexane as beige crystals: TLC (hexane-EtOAc 1:1): Rf=0.42; UPLC RtH5=0.955 min; ESIMS: 406 [(M+H)+]; 1H NMR (360 MHz, CDCl3): δ 6.82 (dd, 1H), 6.52 (m, 2H), 4.30 (dd, 1H), 3.97 (dd, 1H), 3.06 (br s, 2H), 1.58 (s, 3H), 1.48 (s, 3H), 1.46 (s, 9H).

Workup

  1. filtrationThe catalyst was filtered off over Celite
  2. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-c2f20f6d2fa5454396c183e5a2da949c
Source dataset
uspto-grants-2013_09
Patent number
US08524897B2

Reaction notes

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