Potassium Carbonate → Ethyl [5-benzyloxy-4'-(trifluoromethyl)biphenyl-3-yl]acetate

HRID 426304Notes

Reaction equation

HRID 426304 reaction equation
[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]1[CH:11]=[C:10](Br)[CH:9]=[C:8]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:7]=1)[CH3:2].[F:22][C:23]([F:34])([F:33])[C:24]1[CH:29]=[CH:28][C:27](B(O)O)=[CH:26][CH:25]=1.C([O-])([O-])=O.[K+].[K+]>COCCOC>[CH2:1]([O:3][C:4](=[O:21])[CH2:5][C:6]1[CH:11]=[C:10]([C:27]2[CH:28]=[CH:29][C:24]([C:23]([F:34])([F:33])[F:22])=[CH:25][CH:26]=2)[CH:9]=[C:8]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:7]=1)[CH3:2]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27343894-(Trifluoromethyl)phenylboronic acidHCID 66702483(3-Benzyloxy-5-bromophenyl)-acetic acid ethyl ester

Product 1

HCID 24771790Ethyl [5-benzyloxy-4'-(trifluoromethyl)biphenyl-3-yl]acetateYield 74%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

(3-Benzyloxy-5-bromo-phenyl)-acetic acid ethyl ester (2.50 g, 7.2 mmol) was added to a solution of 4-(trifluoromethyl)phenyl boronic acid (1.5 g, 8.0 mmol) and K2CO3 (14.4 mmol, 2 M aq.) in DME (25 mL). Nitrogen was bubbled through the reaction mixture for 10 minutes before addition of tetrakis(triphenylphosphine)palladium(0) (10% wt) and the resultant mixture was heated to 80° C. for 4 hours under inert atmosphere. The reaction mixture was diluted with water and extracted with EtOAc (×3). The combined organic extracts were washed with sat. Na2CO3, brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash column chromatography (EtOAc:petroleum ether) to give (5-benzyloxy-4′trifluoromethyl-biphenyl-3-yl)-acetic acid ethyl ester (2.2 g) as a colourless gum in 74% yield. 1H NMR (CDCl3) δ 7.59-7.54 (m, 2H), 7.48-7.30 (m, 8H), 7.13-7.11 (m, 2H), 6.94-6.91 (m, 1H), 5.12 (s, 2H), 4.16 (q, 2H), 3.64 (s, 2H), 1.27 (t, 3H).

Workup

  1. customNitrogen was bubbled through the reaction mixture for 10 minutes before addition of tetrakis(triphenylphosphine)palladium(0) (10% wt)
  2. additionThe reaction mixture was diluted with water
  3. extractionextracted with EtOAc (×3)
  4. washThe combined organic extracts were washed with sat. Na2CO3, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by flash column chromatography (EtOAc:petroleum ether)

Sources & evidence

ORD record
ord-01f90363f56649bfbcda4904645752f1
Source dataset
uspto-grants-2012_01
Patent number
US08106236B2

Reaction notes

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