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 221498ノート

反応式

HRID 221498 の反応式
[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]

参加物

8

反応物 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、化合物

生成物 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 ester収率 57.8%

試薬・触媒・溶媒 3

HCID 3776Isopropanol溶媒2 回HCID 6344Dichloromethane溶媒HCID 8471Triethylamine溶媒

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-0d36823dee2341a2aaa1a71705d33178
出典データセット
uspto-grants-2012_06
特許番号
US08207161B2

反応ノート

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