Potassium Carbonate → Tert-butyl 4'-methyl-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]biphenyl-3-carboxylate

HRID 888369Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]([CH:12]=[C:13]([C:15]([OH:24])([C:20]([F:23])([F:22])[F:21])[C:16]([F:19])([F:18])[F:17])[CH:14]=1)[C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[CH3:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C([O-])([O-])=O.[K+].[K+]>C(O)CC.O>[CH3:25][C:26]1[CH:31]=[CH:30][C:29]([C:2]2[CH:14]=[C:13]([C:15]([OH:24])([C:20]([F:21])([F:22])[F:23])[C:16]([F:17])([F:19])[F:18])[CH:12]=[C:4]([C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])[CH:3]=2)=[CH:28][CH:27]=1

Participants

Conditions

Temperature: 85 °C

Procedure

To a mixture of tert-butyl 3-bromo-5-[2,2,2-trifluoro-1-hydroxy-1-(trifluoromethyl)ethyl]benzoate (1.2 g, 2.8 mmol) from Example 2.11 step B, (4-methylphenyl)boronic acid (0.5 g, 3.7 mmol), Pd[P(Ph3)]4 (0.16 g, 0.14 mmol), and K2CO3 (1.2 g, 8.5 mmol) under N2 was added 28 mL of degassed n-Propanol/water (4:1). The reaction was heated to 85° C. overnight. The mixture was cooled to room temperature, filtered over celite and concentrated. The crude material was taken up in EtOAc and sat. NaHCO3. The organic layer was extracted (3×) and washed with brine. The final organic layer was dried over Na2SO4, filtered and concentrated to 1.0 g of crude material. Purification using automated flash chromatography (SiO2, 120 g, 0-5% MeOH/DCM) gave, upon concentration, title product.

Workup

temperatureThe mixture was cooled to room temperature
filtrationfiltered over celite and
concentrationconcentrated
extractionThe organic layer was extracted (3×)
washwashed with brine
dry with materialThe final organic layer was dried over Na2SO4
filtrationfiltered
concentrationconcentrated to 1.0 g of crude material
customPurification

Sources & evidence

ORD record: ord-f965fd1624894df19409446d99519014
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08247401B2

Reaction notes

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