Water → 1-((2R,3R,4R)-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-yl)tetrahydro-1H,3H-pyrrolo[1,2-c]oxazol-3-one

HRID 747036ノート

反応式

HRID 747036 の反応式
[H-].[Na+].[F:3][C:4]([F:36])([F:35])[C:5]1[CH:6]=[C:7]([C@H:15]([O:17][C@@H:18]2[C@@H:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[C@H:22]([C@H:30]3CCN3C)[CH2:21][CH2:20][O:19]2)[CH3:16])[CH:8]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:10]=1.[N:37]1([C:42]([O-:44])=[O:43])[CH2:41][CH2:40][CH2:39][CH2:38]1.O>O1CCCC1.C(OCC)(=O)C>[F:13][C:11]([F:12])([F:14])[C:9]1[CH:8]=[C:7]([C@H:15]([O:17][C@@H:18]2[C@@H:23]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[C@H:22]([CH:30]3[O:43][C:42](=[O:44])[N:37]4[CH2:41][CH2:40][CH2:39][CH:38]34)[CH2:21][CH2:20][O:19]2)[CH3:16])[CH:6]=[C:5]([C:4]([F:36])([F:35])[F:3])[CH:10]=1

参加物

7

反応物 4

HCID 962WaterHCID 24758Sodium hydrideHCID 223251731-PyrrolidinecarboxylateHCID 86606931(2R)-2-((2R,3R,4R)-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]ethoxy}-tetrahydro-3-phenyl-2H-pyran-4-yl)-1-methylazetidine

生成物 1

HCID 866069301-((2R,3R,4R)-{(1R)-1-[3,5-Bis(trifluoromethyl)phenyl]-ethoxy}tetrahydro-3-phenyl-2H-pyran-4-yl)tetrahydro-1H,3H-pyrrolo[1,2-c]oxazol-3-one収率 82%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

Sodium hydride (60% dispersion in mineral oil, 15 mg, 0.36 mmol) was added to a solution of 1,1-dimethylethyl (2R or S)-2-[(R or S)-((2R,3R,4R)-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy}tetrahydro-3-phenyl-2H-pyran-4-yl)hydroxymethyl]-1-pyrrolidinecarboxylate (Example 41, Isomer A; 75 mg, 0.12 mmol) in tetrahydrofuran (2 mL) and the mixture was stirred at room temperature for 15 hours. Water (2 mL) was added slowly, then ethyl acetate (10 mL). The layers were separated and the organic layer was washed with brine (5 mL). The combined aqueous layers were extracted with ethyl acetate (10 mL). The combined organic layers were dried (Na2SO4) and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography on silica gel, eluting with hexane/EtOAc (80:20 increasing to 60:40), to give the title compound (Single diastereoisomer; Stereochemistry unassigned) as a colorless foam (54 mg, 82%).

後処理

  1. customThe layers were separated
  2. washthe organic layer was washed with brine (5 mL)
  3. extractionThe combined aqueous layers were extracted with ethyl acetate (10 mL)
  4. dry with materialThe combined organic layers were dried (Na2SO4)
  5. customthe solvent was evaporated under reduced pressure
  6. customThe residue was purified by column chromatography on silica gel
  7. washeluting with hexane/EtOAc (80:20 increasing to 60:40)

出典と根拠

ORDレコード
ord-7b73cda848154340ad522e8a0cfa21aa
出典データセット
uspto-grants-2008_07
特許番号
US07393858B2

反応ノート

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