Hexamethyldisilazane → Rac-2-cyclopentyloxy-2-(3,4-dichloro-phenyl)-acetamide

Temperature

0 °C

A cooled (0° C.) solution of rac-cyclopentyloxy-(3,4-dichloro-phenyl)-acetic acid (Example 1; 164 mg, 0.57 mmol) in dichloromethane (10 mL) and N,N-dimethylformamide (one drop) was treated with oxalyl chloride (2.0 M solution in dichloromethane, 0.43 mL, 0.86 mmol). The reaction was stirred at 0° C. for 1 h, then 1,1,1,3,3,3-hexamethyldisilazane (0.42 mL, 2.0 mmol) was added and the resulting cloudy mixture was stirred at 25° C. for 16 h. The reaction was quenched with methanol (10 mL), washed with an aqueous solution of 5% sulfuric acid (2×15 mL) and extracted with dichloromethane (3×10 mL). The combined organic extracts were washed with brine (1×10 mL), then were dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 60/40 hexanes/ethyl acetate) to give rac-2-cyclopentyloxy-2-(3,4-dichloro-phenyl)-acetamide (116 mg, 71% yield) as a white solid, mp 88.3-91.4° C.; FAB-HRMS m/e calcd for C13H15NCl2O2 (M+) 288.0558, found 288.0572.

1. stirringthe resulting cloudy mixture was stirred at 25° C. for 16 h
2. customThe reaction was quenched with methanol (10 mL)
3. washwashed with an aqueous solution of 5% sulfuric acid (2×15 mL)
4. extractionextracted with dichloromethane (3×10 mL)
5. washThe combined organic extracts were washed with brine (1×10 mL)
6. dry with materialwere dried over magnesium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customThe residue was purified by flash chromatography (Merck Silica gel 60, 230-400 mesh, 60/40 hexanes/ethyl acetate)

ORD record

ord-c7825444f52744d4b5ba9faabf7e209b

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06608218B2