Hexamethylphosphoramide → Methyl 3-cyclopentyl-2-methyl-2-phenylpropanoate

Temperature

0 °C

A solution of lithium bis(trimethylsilyl)amide (1M in tetrahydrofuran, 3.04 mL, 3.04 mmol, 1 equiv) under a N2 atmosphere was cooled to 0° C. and treated with a solution of methyl 2-phenylpropionate (0.500 g, 3.04 mmol, 1 equiv) in dry tetrahydrofuran (2 mL). The reaction was stirred at 0° C. for 2 hrs, then cooled to −78° C. and treated with hexamethylphosphoric triamide (0.4 mL) and bromomethylcyclopentane (0.745 g, 4.568 mmol, 1.5 equiv). Stirred the reaction at −78° C. and allowed the bath to slowly warm to room temperature overnight. After 15 hrs, the reaction mixture was quenched with 10% aq NH4Cl (50 mL) and extracted with ethyl acetate (100 mL). The organic extract was washed with H2O (50 mL) and brine, then dried over Na2SO4, filtered, and concentrated by rotary evaporation. The residue was purified by SiO2 flash chromatography with 2:3 dichloromethane/hexanes to give the product as colorless oil (1.38 g, 5.60 mmol, 92%). 1H NMR (300 MHz, DMSO-d6): δ ppm 0.90-1.12 m, 2 H) 1.32-1.72 m, 10 H) 1.97-2.12 (m, 2H) 3.58 (s, 3 H) 7.19-7.35 m, 5 H); MS (APCI+) m/z 247 (M+H)+.

1. temperaturecooled to −78° C.
2. stirringStirred
3. customthe reaction at −78° C.
4. temperatureto slowly warm to room temperature overnight
5. waitAfter 15 hrs
6. customthe reaction mixture was quenched with 10% aq NH4Cl (50 mL)
7. extractionextracted with ethyl acetate (100 mL)
8. extractionThe organic extract
9. washwas washed with H2O (50 mL) and brine
10. dry with materialdried over Na2SO4
11. filtrationfiltered
12. concentrationconcentrated by rotary evaporation
13. customThe residue was purified by SiO2 flash chromatography with 2:3 dichloromethane/hexanes

ORD record

ord-dec52d53b4d6428b88bc88249268132d

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07378414B2