(R)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)-3-[4-(2-{4-methanesulfonyloxyphenyl}-ethoxy)phenyl]propanoic amide → HCID 20670106, compound

HRID 432072Notes

Reaction equation

HRID 432072 reaction equation
[CH2:1]([O:3][C@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][C:27]2[CH:32]=[CH:31][C:30]([O:33][S:34]([CH3:37])(=[O:36])=[O:35])=[CH:29][CH:28]=2)=[CH:20][CH:19]=1)[C:5]([NH:7][C@H:8]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH2:9][OH:10])=[O:6])[CH3:2]>CCCCCCC>[CH2:1]([O:3][C@@H:4]([CH2:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][CH2:26][C:27]2[CH:28]=[CH:29][C:30]([O:33][S:34]([CH3:37])(=[O:35])=[O:36])=[CH:31][CH:32]=2)=[CH:20][CH:19]=1)[C:5]([NH:7][C@H:8]([C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)[CH2:9][OH:10])=[O:6])[CH3:2]

Participants

3

Reactant 1

HCID 20670105(R)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)-3-[4-(2-{4-methanesulfonyloxyphenyl}-ethoxy)phenyl]propanoic amide

Product 1

HCID 20670106HCID 20670106, compoundYield 38%

Reagents, catalysts & solvents 1

HCID 8900HeptaneSolvent

Procedure

A solution of 2-ethoxy-3-[4-(2-{4-methanesulfonyloxyphenyl} ethoxy)phenyl]propanoic acid (10.5 g; 25.7 mmole) in dry dichloromethane (150 ml) was cooled on an ice-bath and EDC (5.42 g; 28.3 mmole), diisopropylethylamine (4.8 ml; 28.3 mmole) and HOBtxH2O (3.82 g; 28.3 mmole) were added. After 20 minutes the ice-bath was removed and (R)-phenylglycinol (3.88 g; 28.3 mmole) was added. After stirring at room temperature over night dichloromethane (100 ml), citric acid (60 ml, 10%) and ethyl acetate were added and the phases were separated. The organic phase was washed with citric acid (60 ml), sodium bicarbonate (2×60 ml) and brine (60 ml), dried (sodium sulfate), filtered and the solvent evaporated in vacuo. The crude product was crystallized twice in ethyl acetate/heptan to give 4.43 g of (R)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)phenyl]propanoic amide. The mother liquids were combined, the solvent was evaporated in vacuo and the residue was purified by chromatography on silica gel using ethyl acetate:heptan (gradient 25 to 100% ethyl acetate) to give 5.14 g (yield 38%) of (S)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)-3-[4-(2-{4-methanesulfonyloxyphenyl}ethoxy)-phenyl]propanoic amide and 0.51 g (totally 4.94 g, yield 36%) of (R)-2-ethoxy-N-(2-hydroxy-(R)-1-phenylethyl)-3-[4-(2-{4-methanesulfonyloxyphenyl}-ethoxy)phenyl]propanoic amide.

Workup

  1. customthe solvent was evaporated in vacuo
  2. customthe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-b7730eb6305f4cbaa33a5f6e2539062f
Source dataset
uspto-grants-2003_12
Patent number
US06660879B2

Reaction notes

Loading…