Allyl chloroformate → tert-butyl (3S)-3-[[(allyloxy)carbonyl](2-methoxy-2-oxoethyl)amino]-4-(methoxymethoxy)butanoate

HRID 1374431Notes

Reaction equation

HRID 1374431 reaction equation
[NH2:1][C@H:2]([CH2:11][O:12][CH2:13][O:14][CH3:15])[CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:9])[CH3:8])=[O:5].C(N(C(C)C)CC)(C)C.Br[CH2:26][C:27]([O:29][CH3:30])=[O:28].Cl[C:32]([O:34][CH2:35][CH:36]=[CH2:37])=[O:33]>CO.O>[CH2:35]([O:34][C:32]([N:1]([CH2:26][C:27]([O:29][CH3:30])=[O:28])[C@H:2]([CH2:11][O:12][CH2:13][O:14][CH3:15])[CH2:3][C:4]([O:6][C:7]([CH3:10])([CH3:8])[CH3:9])=[O:5])=[O:33])[CH:36]=[CH2:37]

Participants

7

Reactant 4

HCID 18052Allyl chloroformateHCID 60984Methyl bromoacetate2×HCID 81531Diisopropylethylamine3×HCID 58781940Tert-butyl(3s)-3-amino-4-(methoxymethoxy)butanoate

Product 1

HCID 86592529tert-butyl (3S)-3-[[(allyloxy)carbonyl](2-methoxy-2-oxoethyl)amino]-4-(methoxymethoxy)butanoateYield 71%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl(3S)-3-amino-4-(methoxymethoxy)butanoate (9.7 g, 44 mmol) and diisopropylethylamine (11.5 ml, 66 mmol) in methanol (300 ml) was dropped at room temperature methyl bromoacetate (6.2 ml, 66 mmol). The solution was stirred for 1 hour at 60° C. Additional methyl bromoacetate (2.1 ml, 22 mmol) and diisopropylethylamine (3.8 ml, 22 mmol) were added thereto and the mixture was stirred for 1 hour, cooled to room temperature and the solvent was removed. The residue was dissolved in chloroform (100 ml) and thereto were dropped at 0° C. allyl chloroformate (94 ml, 88 mmol) and then diisopropylethylamine (15.5 ml, 88 mmol). The mixture was stirred at the same temperature for 1 hour and at room temperature for 13 hours. To the reaction mixture was added water under cooling in an ice bath and the mixture was extracted three times with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and dried over magnesium sulfate. The residue was purified with silica gel (230 g) chromatography (hexane/ethyl acetate=2/1→1/1) to give tert-butyl (3S)-3-[[(allyloxy)carbonyl](2-methoxy-2-oxoethyl)amino]-4-(methoxymethoxy)butanoate (11.7 g, 71%).

Workup

  1. stirringthe mixture was stirred for 1 hour
  2. temperaturecooled to room temperature
  3. customthe solvent was removed
  4. dissolutionThe residue was dissolved in chloroform (100 ml)
  5. stirringThe mixture was stirred at the same temperature for 1 hour and at room temperature for 13 hours
  6. temperatureunder cooling in an ice bath
  7. extractionthe mixture was extracted three times with chloroform
  8. washThe organic layer was washed with a saturated aqueous sodium chloride solution
  9. dry with materialdried over magnesium sulfate
  10. customThe residue was purified with silica gel (230 g) chromatography (hexane/ethyl acetate=2/1→1/1)

Sources & evidence

ORD record
ord-6100ce6c7f2547c28ca126152ef4ff08
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

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