Cyclobutanone → N-[2-(1-Hydroxycyclobutyl)phenyl]formamide

Sodium hydride (65% dispersion in mineral oil, 71 mg, 1.775 mmol) was suspended in tetrahydrofuran (6 mL), and to this stirred slurry was added dropwise a solution of N-(2-iodophenyl)formamide (250 mg, 1.012 mmol) in tetrahydrofuran (4 mL). The mixture was stirred at room temperature for 20 minutes, then chilled to −78° C. To the cold suspension was added dropwise 2.5 M n-butyllithium in hexanes (0.506 ml, 1.265 mmol). The mixture was stirred at −78° C. for 30 minutes, then cyclobutanone (0.083 ml, 1.113 mmol) was added dropwise. The mixture was stirred at −78° C. for 2 hours and quenched with saturated NH4Cl (20 mL) solution and warmed to room temperature. The mixture was extracted with ethyl acetate (3×30 mL), and the combined organic layers were dried (Na2SO4), filtered, and concentrated. The product was purified by flash chromatography (Analogix, 20 to 50% ethyl acetate-hexanes over 25 min, 4 g silica cartridge, 18 mL/min) to give the title compound as a 2:1 ratio of two rotational isomers.

1. temperaturechilled to −78° C
2. stirringThe mixture was stirred at −78° C. for 30 minutes
3. stirringThe mixture was stirred at −78° C. for 2 hours
4. customquenched with saturated NH4Cl (20 mL) solution
5. temperaturewarmed to room temperature
6. extractionThe mixture was extracted with ethyl acetate (3×30 mL)
7. dry with materialthe combined organic layers were dried (Na2SO4)
8. filtrationfiltered
9. concentrationconcentrated
10. customThe product was purified by flash chromatography (Analogix, 20 to 50% ethyl acetate-hexanes over 25 min, 4 g silica cartridge, 18 mL/min)

ORD record

ord-7b5e3898f8904079b8fcae1b47cac5b6

Source dataset

uspto-grants-2013_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08426408B2