Triethylamine → Ethyl (E)-3-[1-benzyloxy-3-(tert-butoxycarbonylamino)cyclobutan-3-yl]acrylate

HRID 1279646Notes

Reaction equation

HRID 1279646 reaction equation
[CH2:1]([O:8][CH:9]1[CH2:12][C:11]([CH:21](O)[CH2:22][C:23]([O:25][CH2:26][CH3:27])=[O:24])([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CS(Cl)(=O)=O.C(N(CC)CC)C.C1(C2CCCCCCCCCC=2)CCCCCCCCNN=1.[Cl-].[NH4+]>ClCCl.C(OCC)(=O)C>[CH2:1]([O:8][CH:9]1[CH2:12][C:11](/[CH:21]=[CH:22]/[C:23]([O:25][CH2:26][CH3:27])=[O:24])([NH:13][C:14]([O:16][C:17]([CH3:19])([CH3:20])[CH3:18])=[O:15])[CH2:10]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 31297Methanesulfonyl chlorideHCID 18427801Ethyl 3-[1-benzyloxy-3-(tert-butoxycarbonylamino)cyclobutan-3-yl]-3-hydroxypropionateHCID 536302743-(Cycloundecen-1-yl)-1,2-diazacycloundec-2-ene

Product 1

HCID 86758504Ethyl (E)-3-[1-benzyloxy-3-(tert-butoxycarbonylamino)cyclobutan-3-yl]acrylateYield 91.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A 35.61 g (90.50 mmol) portion of ethyl 3-[1-benzyloxy-3-(tert-butoxycarbonylamino)cyclobutan-3-yl]-3-hydroxypropionate was dissolved in 200 ml of dichloromethane to which, while cooling in an ice bath with stirring, were subsequently added 9.050 ml (116.9 mmol) of methanesulfonyl chloride and 37.24 ml (267.2 mmol) of triethylamine in that order. After 2 hours of stirring, to this was added 30.60 ml (204.6 mmol) of diazabicycloundecene. After 1 hour of stirring, the ice bath was detached and the reaction mixture was stirred at room temperature for 2 hours. While cooling in an ice bath with stirring, this was mixed with saturated ammonium chloride aqueous solution and then with ethyl acetate to effect separation of layers. The resulting organic layer was washed with 10% citric acid aqueous solution and then with saturated brine. After extraction of the aqueous layer with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate. After filtration, the solvent was evaporated under a reduced pressure and the resulting residue was purified by a silica gel column chromatography to give 31.07 g (91.4%) of the title compound.

Workup

  1. temperaturewhile cooling in an ice bath
  2. stirringAfter 2 hours of stirring
  3. stirringAfter 1 hour of stirring
  4. stirringthe reaction mixture was stirred at room temperature for 2 hours
  5. temperatureWhile cooling in an ice bath
  6. stirringwith stirring
  7. customseparation of layers
  8. washThe resulting organic layer was washed with 10% citric acid aqueous solution
  9. extractionAfter extraction of the aqueous layer with ethyl acetate
  10. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  11. filtrationAfter filtration
  12. customthe solvent was evaporated under a reduced pressure
  13. customthe resulting residue was purified by a silica gel column chromatography

Sources & evidence

ORD record
ord-7287bcfe75b24889a78a9d0844a1dc1e
Source dataset
uspto-grants-2002_09
Patent number
US06448266B1

Reaction notes

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