Phenylacetylene → (+/-)-(4R*,5R*)-5-((1R*)-1-hydroxy-3-phenylprop-2-ynyl)-1-methyl-4-phenyl-pyrrolidin-2-one

Temperature

-20 °C

To a −20° C. solution of phenylacetylene (0.29 mL, 2.69 mmol) in anhyd. THF (1 mL) was added a solution of n-BuLi (1.6M in hexane, 1.56 mL, 2.50 mmol). The reaction mixture was stirred for 2 h at −20° C., then was cooled to −78° C. A solution of (±)-(4R*,5R*)-5-formyl-1-methyl-4-phenylpyrrolidin-2-one (Intermediate Z, 389 mg, 1.92 mmol) in THF (2 mL) was added dropwise. The reaction mixture was allowed to warm to room temperature, stirred for 18 h, then treated with a saturated NH4Cl solution and extracted with CH2Cl2. The combined organic layers were washed with a saturated NaCl solution, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by flash chromatography (90% EtOAc/hex) to give (±)-(4R*,5R*)-5-((1R*)-1-hydroxy-3-phenylprop-2-ynyl)-1-methyl-4-phenyl-pyrrolidin-2-one (230 mg, 40%) as a white solid: mp 152-153° C.; 1H NMR (CDCl3) δ 2.78-3.09 (m, 5H), 4.02 (q, J=9.0 Hz, 1H), 4.38 (dd, J=9.0 Hz, 2.0 Hz, 1H), 7.22-7.40 (m, 10H), 9.18 (d,J=2.0 Hz, 1H).

1. customTo a −20° C.
2. temperaturewas cooled to −78° C
3. temperatureto warm to room temperature
4. stirringstirred for 18 h
5. extractionextracted with CH2Cl2
6. washThe combined organic layers were washed with a saturated NaCl solution
7. dry with materialdried (Na2SO4)
8. concentrationconcentrated under reduced pressure
9. customThe crude product was purified by flash chromatography (90% EtOAc/hex)

ORD record

ord-e472f64202df46c78ca54b36cf7c5e71

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06784167B2