Phosgene → tert-Butyl N-allyl-N-{[allyl(cyclopropylmethyl)amino]carbonyl}glycinate

HRID 1442869Notes

Reaction equation

HRID 1442869 reaction equation
[CH2:1]([NH:4][CH2:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH:2]=[CH2:3].[C:13](Cl)(Cl)=[O:14].C(N(CC)CC)C.[CH:24]1([CH2:27][NH:28][CH2:29][CH:30]=[CH2:31])[CH2:26][CH2:25]1>C1COCC1.C1(C)C=CC=CC=1>[CH2:1]([N:4]([C:13]([N:28]([CH2:29][CH:30]=[CH2:31])[CH2:27][CH:24]1[CH2:26][CH2:25]1)=[O:14])[CH2:5][C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7])[CH:2]=[CH2:3]

Participants

7

Reactant 4

HCID 6371PhosgeneHCID 8471Triethylamine2×HCID 19959470Tert-butyl 2-[(prop-2-en-1-yl)amino]acetateHCID 20460830N-2-Propen-1-ylcyclopropanemethanamine

Product 1

HCID 18442657tert-Butyl N-allyl-N-{[allyl(cyclopropylmethyl)amino]carbonyl}glycinate

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To an ice-cooled solution of tert-butyl N-allylglycinate (Senokuchi et al. J. Med. Chem. 1995, 38, 2521) (308 mg, 1.80 mmol) in anhydrous THF (10 mL) was added phosgene (0.89 mL of a 20% solution in toluene, 1.80 mmol), then triethylamine (0.25 mL, 1.80 mmol). The resulting solution was stirred at 0° C. for 1 h, then N-(cyclopropylmethyl)prop-2-en-1-amine from Step A (200 mg, 1.80 mmol) was added, followed by triethylamine (0.75 mL, 5.40 mmol). The reaction mixture was allowed to warm to ambient temperature and stirring was continued for 18 h. The solvent was removed under reduced pressure and the residue was partitioned between EtOAc and water. The organic layer was dried over Na2SO4, filtered, and concentrated in vacuo to give a crude product, which was purified by silica gel chromatography, eluting with a gradient of hexane:EtOAc—100:0 to 90:10 to provide the title compound. MS: m/z=309 (M+1).

Workup

  1. temperatureto warm to ambient temperature
  2. stirringstirring
  3. waitwas continued for 18 h
  4. customThe solvent was removed under reduced pressure
  5. customthe residue was partitioned between EtOAc and water
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a crude product, which
  10. customwas purified by silica gel chromatography
  11. washeluting with a gradient of hexane

Sources & evidence

ORD record
ord-4bfd651d5eb8453a818b1240339a761c
Source dataset
uspto-grants-2010_02
Patent number
US07659300B2

Reaction notes

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