Boron tribromide → (+/-)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-hydroxyphenyl)piperidin-1-yl)pyrrolidin-2-one

HRID 1507225Notes

Reaction equation

HRID 1507225 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[CH3:30])[CH2:5][N:6]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([C:17]3[CH:22]=[CH:21][C:20]([O:23]C)=[CH:19][CH:18]=3)[C@H:13]([OH:25])[CH2:12]2)[C:7]1=[O:26].B(Br)(Br)Br>C(Cl)Cl>[F:1][C:2]1[CH:3]=[C:4]([CH:27]=[CH:28][C:29]=1[CH3:30])[CH2:5][N:6]1[CH2:10][CH2:9][CH:8]([N:11]2[CH2:16][CH2:15][C@@H:14]([C:17]3[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=3)[C@H:13]([OH:25])[CH2:12]2)[C:7]1=[O:26]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 118207421(+/-)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)pyrrolidin-2-one

Product 1

HCID 118207433(+/-)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-hydroxyphenyl)piperidin-1-yl)pyrrolidin-2-oneYield 50%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (±)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-methoxyphenyl)piperidin-1-yl)pyrrolidin-2-one (300 mg, 0.73 mmol) in DCM (20 mL) under nitrogen at −10° C. was added boron tribromide (0.17 mL, 1.8 mmol) and the reaction mixture was stirred at rt for 1 h. The reaction was then quenched with saturated sodium bicarbonate solution and extracted with 200 mL of ethyl acetate. The organic layer was separated, dried over Na2SO4, filtered, and evaporated under reduced pressure to give (±)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-hydroxyphenyl)piperidin-1-yl)pyrrolidin-2-one (290 mg, 0.36 mmol, 50% yield, mixture of 4 diastereoisomers); LCMS (Method F) RT 1.854 min m/z 399.2 (M+H+).

Workup

  1. customThe reaction was then quenched with saturated sodium bicarbonate solution
  2. extractionextracted with 200 mL of ethyl acetate
  3. customThe organic layer was separated
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-9cbc4432b3da4d1dbb435d67a8c94389
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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