Cesium fluoride → Ethyl 2-(5-chloro-4'-methyl-6-(2,2,2-trifluoroethoxy) biphenyl-3-yl)-3-cyclopropylpropanoate

HRID 385446Notes

Reaction equation

HRID 385446 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:15]([CH2:21][CH:22]2[CH2:24][CH2:23]2)[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:5]=[C:6]([Cl:14])[C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11].[CH3:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.[F-].[Cs+]>COCCOC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[Cl:14][C:6]1[CH:5]=[C:4]([CH:15]([CH2:21][CH:22]2[CH2:24][CH2:23]2)[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:3]=[C:2]([C:29]2[CH:30]=[CH:31][C:26]([CH3:25])=[CH:27][CH:28]=2)[C:7]=1[O:8][CH2:9][C:10]([F:13])([F:12])[F:11]

Participants

6

Reactant 3

HCID 25953Cesium fluorideHCID 79799Tolylboronic acidHCID 57995641Ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate

Product 1

HCID 57995605Ethyl 2-(5-chloro-4'-methyl-6-(2,2,2-trifluoroethoxy) biphenyl-3-yl)-3-cyclopropylpropanoateYield 74%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of compound ethyl 2-(3-bromo-5-chloro-4-(2,2,2-trifluoroethoxy)phenyl)-3-cyclopropylpropanoate (500 mg, 1.15 mmol), 4-methyl phenylboronic acid (0.237 g, 1.74 mmol), Palladium Tetrakis(triphenylphosphine) (0.134 g, 0.116 mmol), Cesium fluoride (0.354 g, 2.23 mmol) in DME (30 ml) was stirred for overnight at 100° C. After completion of the reaction, the precipitate was removed by filtration. The filtrate was diluted with water and extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with water, brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography to yield ethyl 2-(5-chloro-4′-methyl-6-(2,2,2-trifluoroethoxy) biphenyl-3-yl)-3-cyclopropylpropanoate (375 mg,) as a thick oil.

Workup

  1. customAfter completion of the reaction
  2. customthe precipitate was removed by filtration
  3. additionThe filtrate was diluted with water
  4. extractionextracted with ethyl acetate (2×100 mL)
  5. washThe combined organic layers were washed with water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by column chromatography

Sources & evidence

ORD record
ord-ded5e677ce85455fbc619762eb4d4029
Source dataset
uspto-grants-2013_02
Patent number
US08367863B2

Reaction notes

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