(Diethylamino)sulfur trifluoride → (+/-)-rel-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one

HRID 1507226Notes

Reaction equation

HRID 1507226 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[CH3:29])[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](O)[CH2:12]2)[C:7]1=[O:25].CCN(S(F)(F)[F:36])CC>C(Cl)Cl>[F:36][C@H:13]1[C@H:14]([C:17]2[CH:22]=[CH:21][C:20]([OH:23])=[CH:19][CH:18]=2)[CH2:15][CH2:16][N:11]([CH:8]2[CH2:9][CH2:10][N:6]([CH2:5][C:4]3[CH:26]=[CH:27][C:28]([CH3:29])=[C:2]([F:1])[CH:3]=3)[C:7]2=[O:25])[CH2:12]1

Participants

4

Reactant 2

HCID 123472(Diethylamino)sulfur trifluorideHCID 118207433(+/-)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-hydroxyphenyl)piperidin-1-yl)pyrrolidin-2-one

Product 1

HCID 118207380(+/-)-rel-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-oneYield 7.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (±)-rel-1-(3-fluoro-4-methylbenzyl)-3-((3S,4S)-3-hydroxy-4-(4-hydroxyphenyl)piperidin-1-yl)pyrrolidin-2-one (280 mg, 0.7 mmol) in DCM (20 mL) was added DAST (0.5 mL, 3.5 mmol) and the reaction mixture was stirred under nitrogen for 1 h. The reaction was then quenched by the addition of 100 mL of a saturated sodium bicarbonate solution and the mixture was diluted with 100 mL of ethyl acetate. The organic layer was separated, dried over Na2SO4, filtered, and evaporated under reduced pressure. The residue was subjected to preparative HPLC (method B) to yield 22 mg of (±)-rel-3-((3S,4S)-3-fluoro-4-(4-hydroxyphenyl)piperidin-1-yl)-1-(3-fluoro-4-methylbenzyl)pyrrolidin-2-one as a mixture of 4 diastereomers. LCMS (method P) RT 1.64 min; m/z=401.0 (M+H+).

Workup

  1. customThe reaction was then quenched by the addition of 100 mL of a saturated sodium bicarbonate solution
  2. additionthe mixture was diluted with 100 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-7b2643d21b62468fa04bb4de25995b0d
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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