Cesium carbonate → (S)-3-{4-[2-(4-Difluoromethoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester

HRID 2272836Notes

Reaction equation

HRID 2272836 reaction equation
[CH2:1]([O:3][C:4](=[O:34])[CH2:5][C@@H:6]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]3[N:22]([N:24]=[C:25]([C:27]4[CH:32]=[CH:31][C:30]([OH:33])=[CH:29][CH:28]=4)[N:26]=3)[CH:23]=2)=[CH:12][CH:11]=1)[C:7]#[C:8][CH3:9])[CH3:2].C([O-])([C:37](Cl)([F:39])[F:38])=O.[Na+].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:34])[CH2:5][C@@H:6]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH2:17][C:18]2[CH:19]=[CH:20][C:21]3[N:22]([N:24]=[C:25]([C:27]4[CH:28]=[CH:29][C:30]([O:33][CH:37]([F:39])[F:38])=[CH:31][CH:32]=4)[N:26]=3)[CH:23]=2)=[CH:12][CH:11]=1)[C:7]#[C:8][CH3:9])[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 2734985Sodium chlorodifluoroacetateHCID 136992561(S)-3-{4-[2-(4-Hydroxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester

Product 1

HCID 118129988(S)-3-{4-[2-(4-Difluoromethoxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (S)-3-{4-[2-(4-hydroxy-phenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-ylmethoxy]-phenyl}-hex-4-ynoic acid ethyl ester (0.25 g, 0.54 mmol) in DMF (10 mL) is added sodium chloro difluoro acetate (0.142 g, 1.09 mmol) and cesium carbonate (0.354 g, 1.09 mmol) at 0° C. and the reaction mixture is heated at 80° C. for 4 hours. The reaction mixture is diluted with ice cold water (50 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts are washed with saturated brine solution (20 mL), dried over sodium sulphate, filtered, and evaporated to dryness. The crude material is purified by silica gel (combiflash purifier 40 g redisep column) and is eluted with 45% EtOAc in hexane to give the title compound as a colorless semi solid (0.15 g, 55.5%). LCMS m/z 506 (M+H)+.

Workup

  1. extractionextracted with EtOAc (2×20 mL)
  2. washThe combined organic extracts are washed with saturated brine solution (20 mL)
  3. dry with materialdried over sodium sulphate
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude material is purified by silica gel (combiflash purifier 40 g redisep column)
  7. washis eluted with 45% EtOAc in hexane

Sources & evidence

ORD record
ord-e2087c02a76447b7823754d959f8018a
Source dataset
uspto-grants-2015_09
Patent number
US09120793B2

Reaction notes

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