tert-Butanol → tert-Butyl (1-(4-bromo-3-methylisoxazol-5-yl)cyclopropyl)carbamate

Temperature

100 °C

To a suspension of 1-(4-bromo-3-methylisoxazol-5-yl)cyclopropanecarboxylic acid (1.60 g, 6.50 mmol) and powdered 4 Å molecular sieves (pre-dried-0.767 g, 48% wt) in toluene (15 mL) was sequentially added N,N-diisopropylethylamine (1.50 mL, 8.59 mmol), diphenyl phosphorazidate (1.576 mL, 7.05 mmol), and tert-butanol (16.80 mL, 176 mmol). The reaction vessel was fitted with a reflux condenser and the mixture was heated to 100° C. for 1 h. After 1 h, the reaction mixture was cooled to room temperature and filtered over a plug of Celite. The filter cake was washed with EtOAc (3×), and the filtrate was concentrated to give a brown oil. The oil was purified on Biotage system (5% EtOAc:95% Hexanes to 20% EtOAc:80% Hexanes). The product tert-butyl 1-(4-bromo-3-methylisoxazol-5-yl)cyclopropylcarbamate (1.55 g, 4.89 mmol, 75% yield) was isolated as white crystals after concentration. LC/MS m/z 317 [M+H]+.

1. dry with material4 Å molecular sieves (pre-dried-0.767 g, 48% wt) in toluene (15 mL)
2. customThe reaction vessel was fitted with a reflux condenser
3. temperaturethe reaction mixture was cooled to room temperature
4. filtrationfiltered over a plug of Celite
5. washThe filter cake was washed with EtOAc (3×)
6. concentrationthe filtrate was concentrated
7. customto give a brown oil
8. customThe oil was purified on Biotage system (5% EtOAc:95% Hexanes to 20% EtOAc:80% Hexanes)

ORD record

ord-600e1655b43a471c981299ebcc501338

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796261B2