Ethanolamine → benzyl (1S)-2-[(2-hydroxyethyl)amino]-2-oxo-1-[4-(trifluoromethoxy)benzyl]ethylcarbamate

HRID 1799302Notes

Reaction equation

HRID 1799302 reaction equation
[NH2:1][CH2:2][CH2:3][OH:4].P(C#N)(OCC)(OCC)=O.[CH2:15]([O:22][C:23]([NH:25][C@@H:26]([CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][C:38]([F:41])([F:40])[F:39])=[CH:33][CH:32]=1)[C:27](O)=[O:28])=[O:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(N(CC)CC)C>C(OCC)(=O)C.CN(C=O)C>[OH:4][CH2:3][CH2:2][NH:1][C:27](=[O:28])[C@@H:26]([NH:25][C:23](=[O:24])[O:22][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:30][C:31]1[CH:36]=[CH:35][C:34]([O:37][C:38]([F:40])([F:39])[F:41])=[CH:33][CH:32]=1

Participants

7

Reactant 4

HCID 700EthanolamineHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 69017443N-[(Benzyloxy)carbonyl]-O-(trifluoromethyl)-L-tyrosine

Product 1

HCID 86636534benzyl (1S)-2-[(2-hydroxyethyl)amino]-2-oxo-1-[4-(trifluoromethoxy)benzyl]ethylcarbamateYield 90%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

2-Aminoethanol (1.62 mL, 26.9 mmol) and diethyl cyanophosphate (4.37 mL, 26.9 mmol) were added to a DMF (82 mL) solution of (2S)-2-{[(benzyloxy)carbonyl]amino}-3-[4-(trifluoromethoxy)phenyl]propanoic acid (9.37 g, 24.4 mmol) prepared in Reference Example 6 (6a), at room temperature. Then, to the resulting mixture was dropwise added a DMF (10 mL) solution of triethylamine (3.75 mL, 26.9 mmol) under ice-cooling with stirring over 45 minutes. The mixture was stirred at room temperature for 3 hours, and ethyl acetate (480 mL) was added to this reaction solution. The mixture was sequentially washed with water (480 mL, four times), 1 N sodium hydroxide, water, and saturated brine. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated. The residue was dried under reduced pressure to give 9.36 g of the title compound (white powder, yield: 90%).

Workup

  1. temperaturecooling
  2. stirringThe mixture was stirred at room temperature for 3 hours
  3. washThe mixture was sequentially washed with water (480 mL, four times), 1 N sodium hydroxide, water, and saturated brine
  4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  5. customthe solvent was evaporated
  6. customThe residue was dried under reduced pressure

Sources & evidence

ORD record
ord-ee0fafb5b4c74a34b86a84cb83ed6d54
Source dataset
uspto-grants-2013_01
Patent number
US08344029B2

Reaction notes

Loading…