Methanol → (4R,5R)-5-(hydroxymethyl)-1-methyl-4-phenylpyrrolidin-2-one

To a 0° C. solution of 3-[((2R,3R)-1-methyl-5-oxo-3-phenylpyrrolidin-2-yl)carbonyl](4S)4-benzyl-1,3-oxazolidin-2-one (41.02 g, 0.108 mol) and MeOH (4.83 mL, 0.119 mol, 1.1 equiv) in THF (500 mL) was added LiBH4 (2.60 g, 0.119 mol, 1.1 equiv) in two portions. The reaction was allowed to warm to room temperature and stirred overnight, then cooled to 0° C. and treated with a saturated NH4Cl solution (100 mL). The resulting mixture was concentrated under reduced pressure and the residue was extracted with EtOAc (3×200 mL). The combined organic layers were washed with a saturated NaCl solution (200 mL), dried (Na2SO4) and concentrated under reduced pressure. The crude product was dissolved in a minimal amount of CH2Cl2, then diluted with Et2O. The resulting precipitate was collected by filtration and washed with Et2O to give (4R,5R)-5-(hydroxymethyl)-1-methyl-4-phenylpyrrolidin-2-one (10.4 g, 47%) as a white solid: TLC (5% MeOH/CH2Cl2) Rf 0.48; 1H NMR (CDCl3) δ 2.54 (dd, J=8.4, 16.6 Hz, 1H), 2.79 (s, 1H), 2.90-3.03 (m, 4H), 3.33 (dd, J=8.4, 16.6 Hz, 1H), 3.61-3.83 (m, 3H), 7.25-7.39 (m, 5H); 13C NMR (CDCl3) δ 28.6, 35.6, 41.6, 59.6, 65.5, 127.2, 128.0, 128.7, 137.7, 146.5, 175.2; HPLC ES-MS m/z (rel abundance) 206 (MH+, 100%).

1. temperaturecooled to 0° C.
2. concentrationThe resulting mixture was concentrated under reduced pressure
3. extractionthe residue was extracted with EtOAc (3×200 mL)
4. washThe combined organic layers were washed with a saturated NaCl solution (200 mL)
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated under reduced pressure
7. dissolutionThe crude product was dissolved in a minimal amount of CH2Cl2
8. additiondiluted with Et2O
9. filtrationThe resulting precipitate was collected by filtration
10. washwashed with Et2O

ORD record

ord-9ba006c923f5483caff701a68e6bb813

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06784167B2