Hydrochloric Acid → (+/-)-(4R*,5R*)-5-[(1S*)hydroxy(5-phenyl(2-thienyl))methyl]-4-[4-(hydroxymethyl)-phenyl]-1-methylpyrrolidin-2-one

HRID 1838008Notes

Reaction equation

HRID 1838008 reaction equation
[OH:1][C@H:2]([C:21]1[S:22][C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:24][CH:25]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:15]=[CH:14][C:13]([C:16](OCC)=[O:17])=[CH:12][CH:11]=1.[Li+].[BH4-].Cl.O>C1COCC1>[OH:1][C@H:2]([C:21]1[S:22][C:23]([C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:24][CH:25]=1)[C@@H:3]1[N:7]([CH3:8])[C:6](=[O:9])[CH2:5][C@@H:4]1[C:10]1[CH:11]=[CH:12][C:13]([CH2:16][OH:17])=[CH:14][CH:15]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 4148881Lithium borohydride2×HCID 59066514(+/-)-(4R*,5R*)-5-[(1S*)Hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-(ethoxycarbonyl)-phenyl)-1-methylpyrrolidin-2-one

Product 1

HCID 59066502(+/-)-(4R*,5R*)-5-[(1S*)hydroxy(5-phenyl(2-thienyl))methyl]-4-[4-(hydroxymethyl)-phenyl]-1-methylpyrrolidin-2-oneYield 21.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(±)-(4R*,5R*)-5-[(1S*)Hydroxy(5-phenyl(2-thienyl))methyl]-4-(4-(ethoxycarbonyl)-phenyl)-1-methylpyrrolidin-2-one (0.046 g, 0.106 mmol) was dissolved in THF (1 mL) under Ar. A solution of LiBH4 (2M in THF, 0.10 mL, 0.21 mmol) was added and the resulting mixture was stirred at room temperature for 18 h. Additional LiBH4 solution (0.5 mL, 1.0 mmol) was added and the reaction was stirred for 24 h. The reaction was treated with a 1M HCl solution, followed by water and the resulting mixture was extracted with EtOAc. The combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The crude product was purified by HPLC to yield (±)-(4R*,5R*)-5-[(1S*)hydroxy(5-phenyl(2-thienyl))methyl]-4-[4-(hydroxymethyl)-phenyl]-1-methylpyrrolidin-2-one (9 mg, 20%) as a white solid: mp 205° C.; TLC (EtOAc)Rf 0.24.

Workup

  1. stirringthe reaction was stirred for 24 h
  2. extractionthe resulting mixture was extracted with EtOAc
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product was purified by HPLC

Sources & evidence

ORD record
ord-1cdf56d1d8524d0faedaae303e30d09a
Source dataset
uspto-grants-2004_08
Patent number
US06784167B2

Reaction notes

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