N,N-Diethylethanamine trihydrofluoride → Benzyl (3R,4R)-4-fluoro-3-hydroxypiperidine-1-carboxylate
Reaction equation
[CH:1]12[O:7][CH:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[O:9])[CH2:2]2.[FH:18].F.F.C(N(CC)CC)C>>[F:18][C@@H:6]1[CH2:5][CH2:4][N:3]([C:8]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:9])[CH2:2][C@H:1]1[OH:7]Participants
Conditions
- Temperature
- 100 °C
Procedure
Racemic benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (1.00 g, 4.29 mmol) (AMRI, Syracuse, N.Y. E00017 Lot IN-GBG-A-009B) and triethylamine trihydrofluoride (0.699 mL, 4.29 mmol) were combined in a sealed tube and heated to 100° C. overnight. The reaction was cooled and partitioned between water and EtOAc. The aqueous layer was extracted 3×EtOAc, and the organic layer was washed with water once, saturated aqueous NaCl once, and the organics were dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The material was treated with DCM and purified by silica gel chromatography (80 g column) using 15-50% EtOAc/hexane to give racemic trans-benzyl 4-fluoro-3-hydroxypiperidine-1-carboxylate (0.612 g, 2.42 mmol, 56% yield). MS (ESI, pos. ion) m/z: 254 (M+1).
Workup
- temperatureThe reaction was cooled
- custompartitioned between water and EtOAc
- extractionThe aqueous layer was extracted 3×EtOAc
- washthe organic layer was washed with water once
- dry with materialsaturated aqueous NaCl once, and the organics were dried over anhydrous Na2SO4
- filtrationfiltered
- concentrationconcentrated in vacuo
- additionThe material was treated with DCM
- custompurified by silica gel chromatography (80 g column)
Sources & evidence
- ORD record
- ord-b038f677412f4943a892409b5546ba8c
- Source dataset
- uspto-grants-2015_07
- Patent number
- US09090593B2
Reaction notes
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