Boron tribromide → 3-((3R,4R)-3-Fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one
Reaction equation
[F:1][C@@H:2]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([O:14]C)=[C:10]([F:16])[CH:9]=2)[CH2:6][CH2:5][N:4]([CH:17]2[CH2:21][CH2:20][N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[C:25]([F:30])[CH:24]=3)[C:18]2=[O:31])[CH2:3]1.B(Br)(Br)Br>C(Cl)Cl>[F:1][C@@H:2]1[C@@H:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([F:16])[CH:9]=2)[CH2:6][CH2:5][N:4]([CH:17]2[CH2:21][CH2:20][N:19]([CH2:22][C:23]3[CH:28]=[CH:27][C:26]([CH3:29])=[C:25]([F:30])[CH:24]=3)[C:18]2=[O:31])[CH2:3]1Participants
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 3-((3R,4R)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (diastereomeric pair from step L, 50 mg, 0.12 mmol) in DCM (5 mL) at −78° C. was added boron tribromide (2 mL, 2 mmol, 1 M in DCM) and the resulting mixture was stirred at rt for 3 h. The solvent was evaporated and the residue subjected to preparative HPLC (method D) to yield 20 mg (0.04 mmol, 37%) of 3-((3R,4R)-3-Fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (diastereomeric pair). LCMS (Method K) RT 1.16 min; m/z 419 (M+H+); 1H NMR (400 MHz, methanol-d4) δ ppm 7.22-7.29 (m, 1H) 6.90-7.09 (m, 5H) 4.88-4.96 (m, 1H) 4.49-4.53 (m, 2H), 4.12-4.25 (m, 1H), 4.35-4.42 (m, 1H) 3.98-4.02 (m, 1H) 3.34-3.48 (m, 4H) 3.14-3.21 (m, 1H) 2.98-3.07 (m, 1H) 2.46-2.56 (m, 1H) 2.20-2.30 (m, 5H) 1.98-2.12 (m, 1H).
Workup
- customThe solvent was evaporated
Sources & evidence
- ORD record
- ord-f457a84ac3c649e39336ab8f78afc06a
- Source dataset
- uspto-grants-2015_12
- Patent number
- US09221796B2
Reaction notes
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