Cesium carbonate → Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoate

HRID 1183743Notes

Reaction equation

HRID 1183743 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:14]([CH2:20][CH2:21][O:22][CH3:23])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:5]=[C:6]([Cl:13])[C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1.C([O-])([O-])=O.[Cs+].[Cs+].[F:30][C:31]([F:42])([F:41])[C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>CN(C=O)C.O>[Cl:13][C:6]1[CH:5]=[C:4]([CH:14]([CH2:20][CH2:21][O:22][CH3:23])[C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:3]=[C:2]([C:35]2[CH:36]=[CH:37][C:32]([C:31]([F:42])([F:41])[F:30])=[CH:33][CH:34]=2)[C:7]=1[O:8][CH2:9][CH:10]1[CH2:12][CH2:11]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 57995612Ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methoxybutanoate

Product 1

HCID 57995624Ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4'-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoateYield 45%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of ethyl 2-(3-bromo-5-chloro-4-(cyclopropylmethoxy)-phenyl)-4-methoxybutanoate (2.3 g, 5.660 mmol) in a mixture of DMF (50 mL) and water (5 mL) were added Cs2CO3 (6.4 g, 19.815 mmol), Pd(TPP)4 (1.3 g, 1.120 mmol) and 4-(trifluoromethyl)phenyl boronic acid (1.29 g, 6.780 mmol) at RT under N2 atmosphere and the resulting mixture was stirred at 80° C. for 14 h. After completion of starting material (by TLC), filtered off the catalyst and celite bed was washed with EtOAc and extracted with EtOAc (3×100 mL). Combined organic layers were washed with water (3×50 mL), brine and dried over anhydrous Na2SO4. After filtration and concentration under reduced pressure, the crude material was purified by column chromatography to afford ethyl 2-(5-chloro-6-(cyclopropylmethoxy)-4′-(trifluoromethyl)biphenyl-3-yl)-4-methoxybutanoate (1.2 g) as an off white solid.

Workup

  1. filtrationAfter completion of starting material (by TLC), filtered off the catalyst and celite bed
  2. washwas washed with EtOAc
  3. extractionextracted with EtOAc (3×100 mL)
  4. washCombined organic layers were washed with water (3×50 mL), brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationAfter filtration and concentration under reduced pressure
  7. customthe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-f80b9d6954954dcfaad90512bc76a240
Source dataset
uspto-grants-2014_03
Patent number
US08664249B2

Reaction notes

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