tert-Butanol → Carbamic acid, N-(2,2-dimethyl-3-oxocyclobutyl)-, 1,1-dimethylethyl ester

Temperature

100 °C

To a solution of 2,2-dimethyl-3-oxocyclobutanecarboxylic acid (3.9 g, 27.5 mmol) and TEA (5.75 g, 57 mmol) in toluene (160 mL) was added diphenylphosphoryl azide (11.5 mL, 57 mmol) slowly under cooling in an ice-water bath. The mixture was stirred at 100° C. for 4 h. The reaction mixture was cooled down to room temperature, and tert-butanol (82 mL, 925 mmol) was added. The resulting mixture was refluxed overnight. The reaction mixture was treated with aqueous sodium bicarbonate (150 mL) and the aqueous solution was extracted with ethyl acetate (50 mL×3). The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated under vacuum, the residue was purified by silica gel column chromatography (2-7% ethyl acetate in petroleum ether) to afford the title compound (650 mg, 3.05 mmol, 11% yield) as a yellow oil. 1H NMR (300 MHz, CDCl3) δ (ppm) 4.81-4.70 (m, 1H), 4.05-3.93 (m, 1H), 3.37 (dd, J1=18.0 Hz, J2=9.0 Hz, 1H), 2.89 (dd, J1=18.0 Hz, J2=6.9 Hz, 1H), 1.48 (s, 9H), 1.28 (s, 3H), 1.13 (s, 3H).

1. temperatureunder cooling in an ice-water bath
2. temperatureThe reaction mixture was cooled down to room temperature
3. temperatureThe resulting mixture was refluxed overnight
4. extractionthe aqueous solution was extracted with ethyl acetate (50 mL×3)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationThe filtrate was concentrated under vacuum
9. customthe residue was purified by silica gel column chromatography (2-7% ethyl acetate in petroleum ether)

ORD record

ord-c511c7d9ceea451c9475265f5c4b6fad

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09156798B2