Dimethyl Sulfoxide → tert-Butyl 2-(1-oxoprop-1-yl)-1-oxo-8-azaspiro[4.5]decane-8-carboxylate

Temperature

-78 °C

To a solution of oxalyl chloride (1.6 mL, 18.3 mmol) in dichloromethane (150 mL) at −78° C. was slowly added dimethyl sulfoxide (2.6 mL, 37 mmol). After 5 min, a solution of tert-butyl 2-(1-hydroxyprop-1-yl)-1-oxo-8-azaspiro[4.5]decane-8-carboxylate (4.75 g, 15.3 mmol) from Step H in dichloromethane (40 mL) was added via an addition funnel. The reaction mixture was stirred for 45 min at −78° C. and then triethylamine (10.2 mL, 73.2 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 to afford 4.65 g. The residue was purified by flash chromatography eluting with 15% ethyl acetate in hexanes to give the title compound (3.98 g) as a pink oil.

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. customto afford 4.65 g
12. customThe residue was purified by flash chromatography
13. washeluting with 15% ethyl acetate in hexanes

ORD record

ord-c0879ba6ad3742769d2b05b03691ff97

Source dataset

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07091211B2