tert-Butanol → Cyclobutanecarboxylic acid, 3,3-difluoro-, 1,1-dimethylethyl ester

3,3-difluorocyclobutanecarboxylic acid (1.0 g, 7.3 mmol) was dissolved in DCM (10 mL) and cooled in an ice bath. To the solution was added N,N-dimethylpyridin-4-amine (92 mg, 0.735 mmol) portionwise followed by 2-methylpropan-2-ol (1.1 g, 14.7 mmol) in one portion. A 1M solution of N,N′-dicyclohexylcarbodiimide in DCM (8.1 mL, 8.1 mmol) was added dropwise keeping the temperature below 10° C. The resulting slurry was warmed up to room temperature and stirred for 18 hours. The solid was removed by filtration and the filtrate was washed with 2N aqueous HCl solution (2×15 mL), water (2×15 mL), and then saturated aqueous NaHCO3 solution (2×15 mL). The organic phase was dried over Na2SO4, filtered, and concentrated in vacuo to give 1.49 g of a crude product as a mixture of white solid and yellow oil. To the mixture was added pentane (30 mL) and the mixture as then filtered through a silica gel pad eluting with pentane to give the title compound (896 mg, 63%) as colourless oil.

1. temperaturecooled in an ice bath
2. customthe temperature below 10° C
3. customThe solid was removed by filtration
4. washthe filtrate was washed with 2N aqueous HCl solution (2×15 mL), water (2×15 mL)
5. dry with materialThe organic phase was dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customto give 1.49 g of a crude product
9. additionas a mixture of white solid and yellow oil
10. filtrationthe mixture as then filtered through a silica gel pad
11. washeluting with pentane

ORDレコード

ord-c6d9a8a60039457ead125d990c65e754

出典データセット

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08592629B2