Hydrochloric Acid → (R)-7-[3-tert-butoxycarbonyl-4-(2,4,5-trifluorophenyl)butanoyl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid

HRID 1896097Notes

Reaction equation

HRID 1896097 reaction equation
C(OC(N[C@H:9]([CH2:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[F:39])[CH2:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]2[C:19]([C:26]([F:29])([F:28])[F:27])=[N:20][C:21]([C:22]([O:24]C)=[O:23])=[C:15]2[CH2:14]1)=[O:12])=O)(C)(C)C.[OH-:40].[Na+].Cl.[CH3:43][OH:44]>>[C:31]([O:40][C:43]([C@H:9]([CH2:30][C:31]1[CH:36]=[C:35]([F:37])[C:34]([F:38])=[CH:33][C:32]=1[F:39])[CH2:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]2[C:19]([C:26]([F:27])([F:29])[F:28])=[N:20][C:21]([C:22]([OH:24])=[O:23])=[C:15]2[CH2:14]1)=[O:12])=[O:44])([CH3:36])([CH3:32])[CH3:30]

Participants

5

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 59548953(R)-7-[3-tert-Butoxycarbonylamino-4-(2,4,5-trifluoro-phenyl)-butyryl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid methyl ester

Product 1

HCID 86663124(R)-7-[3-tert-butoxycarbonyl-4-(2,4,5-trifluorophenyl)butanoyl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acidYield 100%

Procedure

Methyl(R)-7-[3-tert-butoxycarbonylamino 5-trifluoro-phenyl)-butyryl]-3-trifluoro methyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-formate 1p (1.8 g, 3.2 mmol) was dissolved in 50 mL of methanol, followed by addition of 10 mL of aqueous sodium hydroxide (4 M). The reaction mixture was stirred for 1 hours. The reaction mixture was adjusted to pH=3-5 with 2 M hydrochloric acid in an ice bath. The mixture was extracted with ethyl acetate (100 mL×3). The combined organic phase was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to obtain the title compound (R)-7-[3-tert-butoxycarbonyl-4-(2,4,5-trifluorophenyl)butanoyl]-3-trifluoromethyl-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazine-1-carboxylic acid 1q (1.76 g, yield 100%) as a light yellow solid. MS m/z (ESI): 550.9 [M+1]. 1H NMR (400 MHz, CD3OD, ppm): δ 7.29-7.23 (m, 1H), 7.121-7.08 (m, 1H), 5.15-5.03 (m, 2H), 4.41-4.06 (m, 5H), 2.98-2.77 (m, 4H), 1.42-1.26 (m, 9H).

Workup

  1. extractionThe mixture was extracted with ethyl acetate (100 mL×3)
  2. dry with materialThe combined organic phase was dried over anhydrous magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9715a1575b104487a2d975093a96254c
Source dataset
uspto-grants-2013_08
Patent number
US08518946B2

Reaction notes

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