Sulfuric Acid → tert-butyl (2S)-4-amino-2-(tert-butoxy)butanoate

HRID 353378Notes

Reaction equation

HRID 353378 reaction equation
S(=O)(=O)(O)O.[NH2:6][CH2:7][CH2:8][C@H:9]([OH:13])[C:10]([OH:12])=[O:11].[CH3:14][C:15](=[CH2:17])[CH3:16]>C(COC)OC>[NH2:6][CH2:7][CH2:8][C@H:9]([O:13][C:15]([CH3:17])([CH3:16])[CH3:14])[C:10]([O:12][C:15]([CH3:16])([CH3:14])[CH3:17])=[O:11]

Participants

5

Reactant 3

HCID 1118Sulfuric AcidHCID 8255IsobutyleneHCID 27339294-Amino-2-hydroxybutyric acid, (S)-(-)-

Product 1

HCID 12992644tert-butyl (2S)-4-amino-2-(tert-butoxy)butanoate

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
-78 °C

Procedure

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 4-amino-(2S)-hydroxybutyric acid (AHBA), and the mixture was then cooled to −78° C. Isobutylene (38 ml) was added thereto, and the tube was sealed, followed by stirring at room temperature for 96 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 250 mg of a yellow oil. The yellow oil was purified by column chromatography on silica gel (30 g, chloroform-methanol-concentrated aqueous ammonia=20:1:0.05→9:2:0.1) to give 37.9 mg of intermediate 3 and 161 mg of intermediate 4.

Workup

  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

Sources & evidence

ORD record
ord-901a6384f43c4029a2e3a8bf3d9746b3
Source dataset
uspto-grants-2004_06
Patent number
US06750219B1

Reaction notes

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