Nitrogen → 2'-Fluoro-2-formyl-5'-methoxy-biphenyl-4-carboxylic acid methyl ester

HRID 404374Notes

Reaction equation

[CH:1]([C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1OS(C(F)(F)F)(=O)=O)[C:6]([O:8][CH3:9])=[O:7])=[O:2].[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+].N#N>COCCOC.[Pd].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>[F:21][C:22]1[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][C:23]=1[C:12]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[CH:1]=[O:2]

Participants

Conditions

Temperature: 95 °C

Procedure

A mixture of methyl 3-formyl-4-(trifluoromethyl-sulfonyloxy)benzoate (T37.2) (7.57 g, 24.2 mmol), 2-fluoro-5-methoxy-phenylboronic acid (commercially available from Sigma-Aldrich, St. Louis, Mo., USA) (12.4 g, 72.7 mmol), Cs2CO3 (27.6 g, 84.9 mmol), and tetrakis(triphenylphosphine) palladium (2.80 g, 2.42 mmol) in 1,2-dimethoxyethane (DME) (75 mL) was degassed with N2 at room temperature The mixture was heated at 95° C. for 9 hours. After removing solvent, the residue was purified by flash chromatography (silica gel, 1:19 EtOAc/hexane) and gave T37.3, a white solid, in 56% yield (2.9 g). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.88 (dd, J=4 Hz, 1H), 8.45 (s, 1H), 8.28 (m, 1H), 7.69 (d, j=8 Hz, 1H), 7.29 (t, J=9 HZ, 1H), 7.08 (m, 2H), 3.92 (s, 3H), 3.79 (s, 3H).

Workup

customAfter removing solvent
customthe residue was purified by flash chromatography (silica gel, 1:19 EtOAc/hexane)
customgave T37.3

Sources & evidence

ORD record: ord-13279d4502df42c99260343d94ce7003
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748462B2

Reaction notes

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