Sulfuric Acid → tert-butyl (2S)-3-amino-2-(tert-butoxy)propanoate

Temperature

-78 °C

The following reaction was carried out in a Fischer-Porter tube. Dimethoxyethane (76 ml) and 3.2 ml of concentrated sulfuric acid were added in that order to 4.0 g of 3-amino-(2S)-hydroxypropionic acid (L-isoserine), and the mixture was then cooled to −78° C. Isobutylene (38 ml) was added thereto, and the tube was sealed, followed by shaking at room temperature for 48 hr. The tube was then slowly opened, and isobutylene was removed by distillation at room temperature. The reaction mixture was then added dropwise to 128 ml of ice water, and the mixture was washed twice with 250 ml of ether, was cooled to 0° C., and was then neutralized with a 6 N aqueous sodium hydroxide solution. Further, solid sodium chloride was added to prepare a saturated solution, and the mixture was extracted four times with 100 ml of chloroform. The chloroform layers were combined, and the combined chloroform layers were dried over anhydrous sodium sulfate and were then concentrated under the reduced pressure to give 640 mg of a yellow oil. The yellow oil was purified by column chromatography on silica gel (64 g, chloroform-methanol-concentrated aqueous ammonia=20:1:0.05→10:1:0.1) to give 191 mg of intermediate 1 and 430 mg of intermediate 2.

1. customThe following reaction
2. customthe tube was sealed
3. customisobutylene was removed by distillation at room temperature
4. additionThe reaction mixture was then added dropwise to 128 ml of ice water
5. washthe mixture was washed twice with 250 ml of ether
6. temperaturewas cooled to 0° C.
7. additionFurther, solid sodium chloride was added
8. customto prepare a saturated solution
9. extractionthe mixture was extracted four times with 100 ml of chloroform
10. dry with materialthe combined chloroform layers were dried over anhydrous sodium sulfate
11. concentrationwere then concentrated under the reduced pressure

ORD record

ord-a47f86f6a4504c92b54ce09ff013666a

Source dataset

uspto-grants-2004_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06750219B1