Sodium hydride → Rac-2-ethoxy-3-[2-methyl-1-(2-phenyl-thiazol-4-ylmethyl)-1h-indol-5-yl]-propionic acid

HRID 2181236Notes

Reaction equation

HRID 2181236 reaction equation
C([O:3][C:4](=[O:20])[CH:5]([O:17][CH2:18][CH3:19])[CH2:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[NH:12][C:11]([CH3:16])=[CH:10]2)C.Cl[CH2:22][C:23]1[N:24]=[C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[S:26][CH:27]=1.[H-].[Na+]>CN(C)C=O.O>[CH2:18]([O:17][CH:5]([CH2:6][C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([CH2:22][C:23]1[N:24]=[C:25]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[S:26][CH:27]=1)[C:11]([CH3:16])=[CH:10]2)[C:4]([OH:3])=[O:20])[CH3:19]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 2369694-(Chloromethyl)-2-phenyl-1,3-thiazoleHCID 69563210HCID 69563210, compound

Product 1

HCID 9979540Rac-2-ethoxy-3-[2-methyl-1-(2-phenyl-thiazol-4-ylmethyl)-1h-indol-5-yl]-propionic acidYield 90.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

0.28 g (1.0 mmol) rac-2-ethoxy-3-(2-methyl-1H-indol-5-yl)-propionic acid ethyl ester (preparation 5) were reacted with 0.23 g (1.1 mmol) 4-chloromethyl-2-phenyl-thiazole in 5 ml N,N-dimethylformamide in the presence of 0.09 g (2.0 mmol) sodium hydride (55%) in mineral oil) at room temperature for 16 hours. The reaction mixture was then diluted with water and extracted with dichloromethane. The combined organic phases were dried over MgSO4 and evaporated. The residue formed was purified by flash-chromatography (silica gel; eluent: gradient of n-heptane and ethyl acetate) to give 0.38 g (90%) of rac-2-ethoxy-3-[2-methyl-1-(2-phenyl-thiazol-4-ylmethyl)-1H-indol-5-yl]-propionic acid as light brown solid.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe combined organic phases were dried over MgSO4
  3. customevaporated
  4. customThe residue formed
  5. customwas purified by flash-chromatography (silica gel; eluent: gradient of n-heptane and ethyl acetate)

Sources & evidence

ORD record
ord-68cb26092b95480481da26761dd226be
Source dataset
uspto-grants-2005_05
Patent number
US06890947B2

Reaction notes

Loading…