Ammonium Chloride → (+/-)-(4R,5R)-5-((1S *)-Hydroxy-2-thienylmethyl)-1-methyl4-phenyl-pyrrolidin-2-one

HRID 1837990Notes

Reaction equation

[S:1]1[CH:5]=[CH:4][CH:3]=[CH:2]1.[Li].[CH:7]([C@@H:9]1[N:13]([CH3:14])[C:12](=[O:15])[CH2:11][C@@H:10]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:8].[NH4+].[Cl-]>C1COCC1>[OH:8][C@H:7]([C:2]1[S:1][CH:5]=[CH:4][CH:3]=1)[C@@H:9]1[N:13]([CH3:14])[C:12](=[O:15])[CH2:11][C@@H:10]1[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a −50° C. solution of lithium thiophene (1M in THF, 170 mL, 170 mmol) was added a solution of (±)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one (Intermediate Z, 127 mmol) in THF (10 mL). The reaction mixture was allowed to warm to 0° C. over 45 min and treated with a saturated NH4Cl solution. The resulting mixture was extracted with EtOAc, dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (67% EtOAc/hex) to give (±)-(4R*,5R*)-5-((1S*)-hydroxy-2-thienylmethyl)-1-methyl-4-phenylpyrrolidin-2-one (9.76 g, 27%): TLC (EtOAc) Rf 0.42.

Workup

extractionThe resulting mixture was extracted with EtOAc
dry with materialdried (MgSO4)
concentrationconcentrated under reduced pressure
customThe crude product was purified by flash chromatography (67% EtOAc/hex)

Sources & evidence

ORD record: ord-a204989fae014c6f9382e8d6ac9655c6
Source dataset: uspto-grants-2004_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06784167B2

Reaction notes

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