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 747036Notes

Reaction equation

HRID 747036 reaction equation
[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

Participants

7

Reactant 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

Product 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-oneYield 82%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-7b73cda848154340ad522e8a0cfa21aa
Source dataset
uspto-grants-2008_07
Patent number
US07393858B2

Reaction notes

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