Water → Methyl 2'-(difluoromethyl)-2-methylbiphenyl-4-carboxylate

HRID 2410542Notes

Reaction equation

HRID 2410542 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1B1OC(C)(C)C(C)(C)O1)[C:5]([O:7][CH3:8])=[O:6].Br[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[CH:28]([F:30])[F:29].[F-].[Cs+].O>O1CCOCC1.CC(OC)(C)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:29][CH:28]([F:30])[C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][C:22]=1[C:11]1[CH:10]=[CH:9][C:4]([C:5]([O:7][CH3:8])=[O:6])=[CH:3][C:2]=1[CH3:1]

Participants

8

Reactant 4

HCID 962WaterHCID 25953Cesium fluorideHCID 27611811-Bromo-2-(difluoromethyl)benzeneHCID 110870242-Methyl-4-methoxycarbonylphenylboronic acid, pinacol ester

Product 1

HCID 66653005Methyl 2'-(difluoromethyl)-2-methylbiphenyl-4-carboxylate

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 15413tert-Butyl methyl etherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (Combiblocks PN-8756, 1.86 g, 6.74 mmol), 1-bromo-2-difluoromethyl-benzene (Fluorochem 023878, 1.67 g, 8.08 mmol), cesium fluoride (3.07 g, 20.2 mmol) and PdCl2(PPh3)2 (142 mg, 0.20 mmol) was prepared in dioxane (20 mL) and water (10 mL) under nitrogen atmosphere. The resulting mixture was heated at 90° C. for 2 hours. The reaction mixture was diluted with MTBE (60 mL), and then washed with water (2×50 mL) and brine (50 mL). The aqueous layers were extracted with MTBE (50 mL). The organic layers were combined, dried (MgSO4) and concentrated under reduced pressure. After purification by flash chromatography (silica, DCM/heptane), the title compound was obtained as a colorless oil (1.42 g, 76%). HPLC (Method A) Rt 5.0 min (purity: 99.1%). 1H NMR (DMSO-d6, 300 MHz) δ 7.93 (s, 1H), 7.84 (dd, J=7.9, 1.4 Hz, 1H), 7.75 (m, 1H), 7.67-7.56 (m, 2H), 7.28 (m, 2H), 6.55 (t, J=54.7 Hz, 1H), 3.88 (s, 3H), 2.06 (s, 3H).

Workup

  1. washwashed with water (2×50 mL) and brine (50 mL)
  2. extractionThe aqueous layers were extracted with MTBE (50 mL)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customAfter purification by flash chromatography (silica, DCM/heptane)

Sources & evidence

ORD record
ord-161b16db5e99426f9706fe4c546fddef
Source dataset
uspto-grants-2014_08
Patent number
US08815919B2

Reaction notes

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