Chloride → methyl 3-{4-[2-(acetylmethylamino)thiazol-5-yl]phenyl}-2(S)-ethoxypropanoate

HRID 2426308Notes

Reaction equation

HRID 2426308 reaction equation
[Cl-].Br[C:3]1[S:7][C:6]([N:8](C)[C:9](=O)C)=[N:5][CH:4]=1.[CH2:13]([O:15][C@@H:16]([CH2:21][C:22]1[CH:27]=[CH:26][C:25](B2OC(C)(C)C(C)(C)O2)=[CH:24][CH:23]=1)[C:17]([O:19][CH3:20])=[O:18])[CH3:14].[F-].[Cs+].CO[CH2:41][CH2:42][O:43]C>>[C:42]([CH2:9][NH:8][C:6]1[S:7][C:3]([C:25]2[CH:24]=[CH:23][C:22]([CH2:21][C@H:16]([O:15][CH2:13][CH3:14])[C:17]([O:19][CH3:20])=[O:18])=[CH:27][CH:26]=2)=[CH:4][N:5]=1)(=[O:43])[CH3:41]

Participants

6

Reactant 5

HCID 312ChlorideHCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 67147803N-(5-Bromothiazol-2-yl)-N-methylacetamideHCID 67147872methyl 2(S)-ethoxy-3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]propanoate

Product 1

HCID 86606237methyl 3-{4-[2-(acetylmethylamino)thiazol-5-yl]phenyl}-2(S)-ethoxypropanoateYield 37%

Conditions

Temperature
80 °C

Procedure

0.2 g (0.3 mmol) of diphenylphosphinoferrocenepalladium chloride (PdCl2dppf) is added to a solution of 1 g (4.5 mmol) of N-(5-bromothiazol-2-yl)-N-methylacetamide, 1.8 g (6.8 mmol) of methyl 2(S)-ethoxy-3-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)phenyl]propanoate and 1 g (6.8 mmol) of caesium fluoride in 50 ml of ethylene glycol dimethyl ether, degassed beforehand. The reaction medium is heated at 80° C. for 18 hours. After cooling, water is added and the reaction medium is extracted with ethyl acetate. The ethyl acetate phase is washed with saturated sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with a 70/30 and then 60/40 heptane/ethyl acetate mixture. 0.6 g (37%) of methyl 3-{4-[2-(acetylmethylamino)thiazol-5-yl]phenyl}-2(S)-ethoxypropanoate is obtained in the form of a beige-colored solid with a melting point of 123° C.

Workup

  1. customdegassed beforehand
  2. temperatureAfter cooling
  3. additionwater is added
  4. extractionthe reaction medium is extracted with ethyl acetate
  5. washThe ethyl acetate phase is washed with saturated sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue obtained
  10. customis purified by chromatography on a column of silica
  11. washeluted with a 70/30

Sources & evidence

ORD record
ord-33f4ef09b01f40619de3308048ba19d6
Source dataset
uspto-grants-2011_06
Patent number
US07968560B2

Reaction notes

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