Dimethyl Sulfoxide → tert-Butyl 4-methoxy4-(1,3-dioxopent-1-yl)piperidine-1-carboxylate

Temperature

-78 °C

To a solution of oxalyl chloride (0.168 mL, 1.92 mmol) in dichloromethane (10 mL) at −78° C. was slowly added dimethyl sulfoxide (0.272 mL, 3.84 mmol). After 5 min, a solution of tert-butyl 4-(3-hydroxy-1-oxopent-1-yl)-4-methoxypiperidine-1-carboxylate (0.404 g, 1.28 mmol) from Step B in dichloromethane (5 mL) was added via syringe. The reaction mixture was stirred for 45 min at -78° C. and then triethylamine (1.1 mL, 7.68 mmol) was added. After 5 min, the reaction mixture was removed from the cooling bath, allowed to warm to room temperature for 1.5 h, poured into water, and extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography eluting with 10% ethyl acetate/hexanes to afford the title compound (0.227 g).

1. customat −78° C.
2. waitAfter 5 min
3. customthe reaction mixture was removed from the cooling bath
4. temperatureto warm to room temperature for 1.5 h
5. additionpoured into water
6. extractionextracted three times with dichloromethane
7. washwashed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customThe residue was purified by flash chromatography
12. washeluting with 10% ethyl acetate/hexanes

ORD record

ord-2abda1273cd6457e8d73afd6e5bd1098

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07091211B2