Boron tribromide → 3-((3S,4S)-3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methyl-benzyl)pyrrolidin-2-one

HRID 1507210Notes

Reaction equation

HRID 1507210 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]1

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 1182074923-((3S,4S)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)-pyrrolidin-2-one2×

Product 1

HCID 1182073023-((3S,4S)-3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methyl-benzyl)pyrrolidin-2-oneYield 34%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a stirring solution of 3-((3S,4S)-3-fluoro-4-(3-fluoro-4-methoxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one (60 mg, 0.14 mmol, diastereomeric mixture from step H) in 10 mL of DCM at −78° C. was added 2.5 mL of boron tribromide (2.5 mmole) and the mixture allowed to warm to rt and stirred for 3 h. The reaction mixture was then cooled to 0° C. and quenched with saturated NaHCO3 solution. The mixture was then diluted with DCM and the organic layer was separated and evaporated under reduced pressure. The crude compound was purified by preparative HPLC to give 3-((3S,4S)-3-fluoro-4-(3-fluoro-4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methyl-benzyl)pyrrolidin-2-one (20 mg, 0.047 mmol, 34% yield) (diastereomeric pair). LCMS (Method Q) RT=1.17 min, m/z 419.0 (M+H+).

Workup

  1. temperatureThe reaction mixture was then cooled to 0° C.
  2. customquenched with saturated NaHCO3 solution
  3. additionThe mixture was then diluted with DCM
  4. customthe organic layer was separated
  5. customevaporated under reduced pressure
  6. customThe crude compound was purified by preparative HPLC

Sources & evidence

ORD record
ord-d5b5862f2113453b85c56681055ff1d5
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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