Cesium carbonate → tert-Butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionate

HRID 1394007Notes

Reaction equation

HRID 1394007 reaction equation
Br[CH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].C(=O)([O-])[O-].[Cs+].[Cs+].C([N:20]([C:33]([O:35][CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=[O:34])[C@H:21]([C:30]([OH:32])=[O:31])[CH2:22][C:23]1[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=1)(C)(C)C>CC(C)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>[CH2:36]([O:35][C:33]([NH:20][C@@H:21]([CH2:22][C:23]1[CH:24]=[CH:25][C:26]([O:29][CH2:2][CH2:3][CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6])=[CH:27][CH:28]=1)[C:30]([O:32][C:23]([CH3:28])([CH3:24])[CH3:22])=[O:31])=[O:34])[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonate2×HCID 76300Ethyl 4-bromobutyrate4×HCID 69208336tert-butyl N-benzyloxycarbonyltyrosine

Product 1

HCID 11038228tert-Butyl (2S)-2-benzyloxycarbonylamino-3-(4-(3-ethoxycarbonylpropyloxy)phenyl)propionateYield 222.7%

Reagents, catalysts & solvents 2

HCID 10796Cesium carbonateCatalystHCID 180AcetoneSolvent

Procedure

8.29 ml (57.9 mmol) of ethyl 4-bromobutanoate and 28.21 g (86.58 mmol) of cesium carbonate were added to 21.5 g (57.9 mmol) of tert-butyl N-benzyloxycarbonyltyrosine in 280 ml of acetone and the mixture was heated to reflux with stirring. After 2 h, a further 2 ml of ethyl 4-bromobutanoate and 2 g of cesium carbonate were added, after a further 2 h a further 2 ml of ethyl 4-bromobutanoate and 3 g of cesium carbonate were added and after standing at room temperature overnight 9 ml of ethyl 4-bromobutanoate were added again and the mixture was heated to reflux for a further 6 h. After cooling, it was filtered, the residue was washed with acetone and the filtrate was concentrated. The residue was taken up in diethyl ether and the organic phase was washed successively with 3% strength citric acid solution, 3×H2O and saturated NaCl solution. The ether phase was dried over MgSO4, the drying agent was filtered off and the filtrate was concentrated in vacuo. The residue was chromatographed on silica gel using CH2Cl2 and CH2Cl2/MeOH (99/1). 31.3 g of a pale yellow oil were obtained, which was employed without further purification for the synthesis of (1.2).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux
  3. additionwere added
  4. waitafter standing at room temperature overnight
  5. temperaturethe mixture was heated
  6. temperatureto reflux for a further 6 h
  7. temperatureAfter cooling
  8. filtrationit was filtered
  9. washthe residue was washed with acetone
  10. concentrationthe filtrate was concentrated
  11. washthe organic phase was washed successively with 3% strength citric acid solution, 3×H2O and saturated NaCl solution
  12. dry with materialThe ether phase was dried over MgSO4
  13. filtrationthe drying agent was filtered off
  14. concentrationthe filtrate was concentrated in vacuo
  15. customThe residue was chromatographed on silica gel

Sources & evidence

ORD record
ord-f8107a503fc4468db8572eef3e699f70
Source dataset
uspto-grants-2008_03
Patent number
US07348333B2

Reaction notes

Loading…