Lithium borohydride → rac-(4R,5S)-4-(hydroxymethyl)-1-(4-methoxybenzyl)-5-methylpyrrolidin-2-one

HRID 595217Notes

Reaction equation

HRID 595217 reaction equation
[BH4-].[Li+].[CH3:3][O:4][C:5]1[CH:23]=[CH:22][C:8]([CH2:9][N:10]2[C:14](=[O:15])[CH2:13][CH:12]([C:16](OCC)=[O:17])[CH:11]2[CH3:21])=[CH:7][CH:6]=1>C1COCC1>[OH:17][CH2:16][CH:12]1[CH:11]([CH3:21])[N:10]([CH2:9][C:8]2[CH:7]=[CH:6][C:5]([O:4][CH3:3])=[CH:23][CH:22]=2)[C:14](=[O:15])[CH2:13]1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 118208506ethyl rac-(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidine-3-carboxylate

Product 1

HCID 118208939rac-(4R,5S)-4-(hydroxymethyl)-1-(4-methoxybenzyl)-5-methylpyrrolidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Lithium borohydride (3.5 g, 0.16 mol) in THF (50 mL) was slowly added dropwise to a solution of ethyl rac-(2R,3S)-1-(4-methoxybenzyl)-2-methyl-5-oxopyrrolidine-3-carboxylate (18.5 g, 0.064 mol) in THF (350 mL) at 0° C. The reaction mixture was allowed to stir at room temperature for 16 hours and then quenched by the slow addition of saturated aqueous ammonium chloride solution (30 mL). After removal of THF under reduced pressure, the mixture was diluted with water (100 mL) and extracted with ethyl acetate (300 mL×3). The combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether) to give rac-(4R,5S)-4-(hydroxymethyl)-1-(4-methoxybenzyl)-5-methylpyrrolidin-2-one. MS ESI calc'd. for C14H20NO3 [M+H]+ 250. found 250. 1H NMR (CDCl3, 400 MHz): δ 7.10 (d, J=8.4 Hz, 2H), 6.79 (d, J=8.4 Hz, 2H), 4.83 (d, J=14.8 Hz, 1H), 3.85 (d, J=14.8 Hz, 1H), 3.74 (s, 3H), 3.47 (d, J=6.4 Hz, 2H), 3.30-3.27 (m, 1H), 2.76 (s, br, 1H), 2.58-2.52 (m, 1H), 2.24-2.18 (m, 1H), 2.06-2.02 (m, 1H), 1.15 (d, J=6.4 Hz, 3H).

Workup

  1. customquenched by the slow addition of saturated aqueous ammonium chloride solution (30 mL)
  2. customAfter removal of THF under reduced pressure
  3. additionthe mixture was diluted with water (100 mL)
  4. extractionextracted with ethyl acetate (300 mL×3)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by chromatography on silica gel (ethyl acetate/petroleum ether)

Sources & evidence

ORD record
ord-48d31dc9abba44af93499d082419d049
Source dataset
uspto-grants-2016_01
Patent number
US09242984B2

Reaction notes

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