Tetrahydrofuran → trans-4-benzyl-5,5-difluorohexahydrocyclopenta[b][1,4]oxazin-3(2H)-one
Reaction equation
[CH2:1]([N:8]([C@H:13]1[C@H:17]([OH:18])[CH2:16][CH2:15][C:14]1([F:20])[F:19])[C:9](=[O:12])[CH2:10]Cl)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC([O-])(C)C.[K+].C1COCC1>CC(O)(C)C>[CH2:1]([N:8]1[C:9](=[O:12])[CH2:10][O:18][C@@H:17]2[CH2:16][CH2:15][C:14]([F:20])([F:19])[C@@H:13]12)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1Participants
5
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 20 °C
Procedure
To a stirred solution of trans-N-benzyl-2-chloro-N-(2,2-difluoro-5-hydroxycyclopentyl)acetamide (750 mg, 2.46 mmol) in t-BuOH (20 mL) was added a 1M solution of KOtBu in THF (4.93 mL, 4.93 mmol) at 20° C. The reaction mixture was stirred at 20° C. for 2 hours and then the solvent was evaporated under reduced pressure. The residue was dissolved in EtOAc (20 mL), washed with brine (10 mL), dried over anhydrous Na2SO4, and concentrated under reduced pressure. Purification of the residue on a silica gel column (0 to 40% EtOAc/hexanes) afforded trans-4-benzyl-5,5-difluorohexahydrocyclopenta[b][1,4]oxazin-3(2H)-one. MS ESI calc'd. for C14H15F2NO2 [M+H]+ 268. found 268.
Workup
- customthe solvent was evaporated under reduced pressure
- dissolutionThe residue was dissolved in EtOAc (20 mL)
- washwashed with brine (10 mL)
- dry with materialdried over anhydrous Na2SO4
- concentrationconcentrated under reduced pressure
- customPurification of the residue on a silica gel column (0 to 40% EtOAc/hexanes)
Sources & evidence
- ORD record
- ord-bb1d76f8902742ecb170089aee2e7571
- Source dataset
- uspto-grants-2015_02
- Patent number
- US08962611B2
Reaction notes
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