Cesium carbonate → Ethyl (3S)-3-[4-[(2-bromo-[1,2,4]triazolo[1,5-a]pyridin-6-yl)methoxy]phenyl]hex-4-ynoate

HRID 2272832Notes

Reaction equation

HRID 2272832 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:15]#[C:16][CH3:17])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[Br:24][C:25]1[N:35]=[C:28]2[CH:29]=[CH:30][C:31]([CH2:33]Cl)=[CH:32][N:27]2[N:26]=1>CN(C=O)C>[Br:24][C:25]1[N:35]=[C:28]2[CH:29]=[CH:30][C:31]([CH2:33][O:1][C:2]3[CH:3]=[CH:4][C:5]([C@@H:8]([C:15]#[C:16][CH3:17])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=3)=[CH:32][N:27]2[N:26]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 67087065Ethyl (3S)-3-(4-hydroxyphenyl)hex-4-ynoateHCID 1181299662-Bromo-6-(chloromethyl)-[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 118151365Ethyl (3S)-3-[4-[(2-bromo-[1,2,4]triazolo[1,5-a]pyridin-6-yl)methoxy]phenyl]hex-4-ynoateYield 54%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (S)-ethyl 3-(4-hydroxyphenyl)hex-4-ynoate (1.4 g, 6.09 mmol) in DMF, is added cesium carbonate (5.9 g, 18.1 mmol) and 2-bromo-6-(chloromethyl)-[1,2,4]triazolo[1,5-a]pyridine (1.5 g, 6.09 mmol) and the reaction mixture is stirred at room temperature for 2 hours. The reaction mixture is quenched with ice cold water and extracted with EtOAc (2×200 mL). The organic extract is washed with brine (2×30 mL), dried over sodium sulphate, and concentrated. The crude material is purified by silica gel chromatography (combiflash purifier 10 g redisep column) eluting with 25% EtOAc in hexane to give the title compound as a yellow sticky oil (1.4 g, 54%). LCMS m/z 442 (M+H)+.

Workup

  1. customThe reaction mixture is quenched with ice cold water
  2. extractionextracted with EtOAc (2×200 mL)
  3. extractionThe organic extract
  4. washis washed with brine (2×30 mL)
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. customThe crude material is purified by silica gel chromatography (combiflash purifier 10 g redisep column)
  8. washeluting with 25% EtOAc in hexane

Sources & evidence

ORD record
ord-80bb1ff248324232a736429075f91210
Source dataset
uspto-grants-2015_09
Patent number
US09120793B2

Reaction notes

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