Allyl chloroformate → HCID 10894411, compound

HRID 1374409Notes

Reaction equation

HRID 1374409 reaction equation
[NH2:1][C@@H:2]([CH2:12][O:13][CH2:14][O:15][CH3:16])[CH2:3][CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].C(N(C(C)C)CC)(C)C.Br[CH2:27][C:28]([O:30][CH3:31])=[O:29].Cl[C:33]([O:35][CH2:36][CH:37]=[CH2:38])=[O:34]>CO.O>[CH2:36]([O:35][C:33]([N:1]([CH2:27][C:28]([O:30][CH3:31])=[O:29])[C@@H:2]([CH2:12][O:13][CH2:14][O:15][CH3:16])[CH2:3][CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6])=[O:34])[CH:37]=[CH2:38]

Participants

7

Reactant 4

HCID 18052Allyl chloroformateHCID 60984Methyl bromoacetate2×HCID 81531Diisopropylethylamine3×HCID 58781932HCID 58781932, compound

Product 1

HCID 10894411HCID 10894411, compoundYield 77.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of tert-butyl (4R)-4-amino-5-(methoxymethoxy)pentanoate (2.33 g, 10 mmol) and diisopropylethylamine (2.6 ml, 15 mmol) in methanol (70 ml) was dropped at room temperature methyl bromoacetate (1.4 ml, 15 mmol) in methanol (10 ml) and the mixture was stirred at 60° C. for 1 hour. Thereto were added additional methyl bromoacetate (0.5 ml, 5 mmol) and diisopropylethylamine (0.9 ml, 5 mmol). After stirring for 1 hour, the mixture was cooled to room temperature and the solvent was removed in vacuo. The residue was dissolved in chloroform (50 ml) and thereto was dropped allyl chloroformate (2.15 ml, 20 mmol) and then diisopropylethylamine (3.5 ml, 20 mmol). The mixture was stirred at the same temperature for 1 hour and at room temperature for 1 hour, respectively. Water was added thereto under cooling in an ice bath. The mixture was extracted three times with chloroform. The organic layer was washed with a saturated aqueous sodium chloride solution and was dried over magnesium sulfate. The solvent was removed under reduced pressure, and the residue was purified by silica gel (51 g) chromatography (hexane/ethyl acetate: 2/1˜hexane/ethyl acetate: 1/1) to give tert-butyl (4R)-4-[[(allyloxy)carbonyl](2-methoxy-2-oxoethyl)amino}-5-(methoxymethoxy)pentanoate (3.01 g, 77%).

Workup

  1. stirringAfter stirring for 1 hour
  2. temperaturethe mixture was cooled to room temperature
  3. customthe solvent was removed in vacuo
  4. dissolutionThe residue was dissolved in chloroform (50 ml)
  5. stirringThe mixture was stirred at the same temperature for 1 hour and at room temperature for 1 hour
  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 materialwas dried over magnesium sulfate
  10. customThe solvent was removed under reduced pressure
  11. customthe residue was purified by silica gel (51 g) chromatography (hexane/ethyl acetate: 2/1˜hexane/ethyl acetate: 1/1)

Sources & evidence

ORD record
ord-a9239f9ce55e49abb8e688c8499c9840
Source dataset
uspto-grants-2007_01
Patent number
US07163936B2

Reaction notes

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