Sodium hydride → (4-{Tert-butoxycarbonyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl ester

HRID 1393089Notes

Reaction equation

HRID 1393089 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:9][CH:8]=1)[CH3:2].Cl[CH2:23][C:24]1[S:28][C:27]([C:29]2[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=2)=[N:26][CH:25]=1.[H-].[Na+].OS([O-])(=O)=O.[K+].[CH3:47]C(N(C)C)=O>>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N:13]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:23][C:24]2[S:28][C:27]([C:29]3[CH:34]=[CH:33][C:32]([C:35]([F:38])([F:37])[F:36])=[CH:31][CH:30]=3)=[N:26][C:25]=2[CH3:47])=[CH:9][CH:8]=1)[CH3:2]

Participants

6

Reactant 5

HCID 24758Sodium hydrideHCID 31374DimethylacetamideHCID 516920Potassium bisulfateHCID 22647608Thiazole, 5-(chloromethyl)-2-[4-(trifluoromethyl)phenyl]-HCID 54043329Ethyl 2-(4-{[(tert-butoxy)carbonyl]amino}phenoxy)acetate

Product 1

HCID 69218280(4-{Tert-butoxycarbonyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl esterYield 38%

Procedure

To an ice-cooled and stirred solution of (4-tert-butoxycarbonylamino-phenoxy)-acetic acid ethyl ester (0.295, 1 mmol) and 5-chloromethyl-2-(4-trifluoromethyl-phenyl)-thiazole (0.292, 1 mmol) in DMA (10 ml) was added NaH (55% in oil, 0.065 g, 1.5 mmol). The reaction was warmed up and stirred for 5 h at RT, neutralized at 0° C. with aqueous 10% KHSO4 and extracted with aqueous 10% KHSO4/Et2O (3×). The organic phases were washed with aqueous 10% NaCl, dried (Na2SO4) and evaporated. Purification by flash chromatography with a gradient of CH2Cl2:Et2O 99:1 to 98:2 yielded 0.207 g (38%) of (4-{tert-butoxycarbonyl-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-ylmethyl]-amino}-phenoxy)-acetic acid ethyl ester as a yellow viscous oil, MS: 551 (MH+).

Workup

  1. temperatureThe reaction was warmed up
  2. extractionextracted with aqueous 10% KHSO4/Et2O (3×)
  3. washThe organic phases were washed with aqueous 10% NaCl
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. customPurification by flash chromatography with a gradient of CH2Cl2:Et2O 99:1 to 98:2

Sources & evidence

ORD record
ord-cec96babe5e442cb97e2e2c2e670e2dd
Source dataset
uspto-grants-2008_03
Patent number
US07345067B2

Reaction notes

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