Ammonium Chloride → (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 isopropyl ester

HRID 221498노트

반응식

HRID 221498 반응식
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH2:29][C:30]1[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=1[F:38])[CH2:10][C:11]([N:13]1[CH2:18][CH2:17][N:16]2[C:19]([C:25]([F:28])([F:27])[F:26])=[N:20][C:21]([C:22]([OH:24])=[O:23])=[C:15]2[CH2:14]1)=[O:12])=[O:7])([CH3:4])([CH3:3])[CH3:2].O=C1N(P(Cl)(N2CCOC2=O)=O)CCO1.[CH:54](O[Na])([CH3:56])[CH3:55].[Cl-].[NH4+]>C(O)(C)C.C(N(CC)CC)C.ClCCl>[CH:54]([O:23][C:22]([C:21]1[N:20]=[C:19]([C:25]([F:27])([F:28])[F:26])[N:16]2[CH2:17][CH2:18][N:13]([C:11](=[O:12])[CH2:10][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:29][C:30]3[CH:35]=[C:34]([F:36])[C:33]([F:37])=[CH:32][C:31]=3[F:38])[CH2:14][C:15]=12)=[O:24])([CH3:56])[CH3:55]

참가 물질

8

반응물 4

HCID 25517Ammonium ChlorideHCID 152842Bis(2-oxo-3-oxazolidinyl)phosphinic chlorideHCID 59548952(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 acidHCID 178459997HCID 178459997, 화합물

생성물 1

HCID 59548961(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 isopropyl ester수율 57.8%

시약·촉매·용매 3

HCID 3776Isopropanol용매2회HCID 6344Dichloromethane용매HCID 8471Triethylamine용매

실험 절차

(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 2a (0.3 g, 0.54 mmol) was added into a 50 mL reaction flask, followed by addition of 10 mL of dichloromethane, 2 mL of isopropanol and 0.3 mL of triethylamine. After stirring for 1 minutes, bis(2-oxo-3-oxazolidinyl)phosphinic chloride (0.277 g, 1.09 mmol) was added to the solution. The reaction mixture was stirred at room temperature for 2 hours, and then 10 mL of isopropanol and isopropoxysodium (0.177 g, 2.16 mmol) were added. The reaction mixture was stirred at room temperature for 1.5 hours and monitored by thin layer chromatography until the disappearance of the starting materials. 10 mL of saturated ammonium chloride was added to the reaction mixture, and white precipitates were formed. The precipitates were filtered through a pad of silica gel, and 50 mL of water was added to the filtrate. The filtrate was extracted with ethyl acetate (25 mL×5), and the combined organic phase was washed with 30 mL of saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (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 isopropyl ester 35a (0.185 g, yield 57.8%) as a white solid.

후처리

  1. stirringThe reaction mixture was stirred at room temperature for 2 hours
  2. stirringThe reaction mixture was stirred at room temperature for 1.5 hours
  3. customwhite precipitates
  4. customwere formed
  5. filtrationThe precipitates were filtered through a pad of silica gel, and 50 mL of water
  6. additionwas added to the filtrate
  7. extractionThe filtrate was extracted with ethyl acetate (25 mL×5)
  8. washthe combined organic phase was washed with 30 mL of saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe resulting residue was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-0d36823dee2341a2aaa1a71705d33178
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207161B2

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