Hydrochloric Acid → 1-[4-(4-Fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-2-hydroxy-ethanone

To a solution of glycolic acid (0.70 g, 9.2 mmol), 4-dimethylaminopyridine (catalytic) and pyridine (1.52 mL, 18.6 mmol) in dry dichloromethane (20 mL) was added trimethylsilylchloride (2.39 mL, 2.05 mmol) dropwise. The reaction was stirred at ambient temperature for 4 hours. The reaction was then cooled to 0° C. and catalytic dimethylformamide (3 drops) was added followed by addition of oxalyl chloride. The reaction was stirred at 0° C. for one hour and then 30 minutes at ambient temperature. The reaction was cooled back to 0° C. and (3R)-1-(4-fluoro-benzyl)-3-methyl-piperazine (2.11 g, 10.12 mmol) was added as a solution in pyridine (2.45 mL, 30.4 mmol). The reaction was allowed to warm to ambient temperature and stirred for 2 hours. The reaction was neutralized with 1N hydrochloric acid and extracted with dichloromethane (2×). The organic layers were combined, dried over magnesium sulfate, filtered and concentrated in vacuo. Chromatography on silica gel gave the title compound (1.84 g).

1. temperatureThe reaction was then cooled to 0° C.
2. stirringThe reaction was stirred at 0° C. for one hour
3. custom30 minutes
4. customat ambient temperature
5. temperatureThe reaction was cooled back to 0° C.
6. temperatureto warm to ambient temperature
7. stirringstirred for 2 hours
8. extractionextracted with dichloromethane (2×)
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo

ORDレコード

ord-35a0ff1267624cbf982c30cd75644ab8

出典データセット

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07098212B2