Acetaldehyde → Methyl 1-(1-hydroxyethyl)-3,3-dimethoxycyclobutanecarboxylate

Temperature

0 °C

To a solution of diisopropylamine (3.2 mL, 22.67 mmol) in THF (45 mL) was added n-BuLi (2.69 M in hexane, 7.7 mL, 20.71 mmol) at −78° C. under argon. The mixture was stirred for 10 minutes at 0° C., then cooled to −78° C. and added a solution of methyl 3,3-dimethoxycyclobutanecarboxylate (3.0 g, 17.22 mmol) in THF (10 mL). The mixture was stirred for 30 minutes at −78° C., then added a solution of acetaldehyde (1.9 mL, 33.86 mmol) in THF (10 mL). The mixture was stirred for 30 minutes at −78° C., and water was added. The aqueous layer was extracted with EtOAc. Combined organic layers were washed with brine, dried over Na2SO4, filtered, and evaporated under reduced pressure to give methyl 1-(1-hydroxyethyl)-3,3-dimethoxycyclobutanecarboxylate (3.33 g).

1. temperaturecooled to −78° C.
2. stirringThe mixture was stirred for 30 minutes at −78° C.
3. stirringThe mixture was stirred for 30 minutes at −78° C.
4. extractionThe aqueous layer was extracted with EtOAc
5. washCombined organic layers were washed with brine
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. customevaporated under reduced pressure

ORD record

ord-6bbb94ad91dc4247a6febf44a6d922aa

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975415B2