Triphenylphosphine → 6-(4-Fluoro-benzyl)-3-methoxy-2-(3-trifluoromethyl-phenyl)-pyridine

HRID 1632016Notes

Reaction equation

Br[CH2:2][C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=2)[C:6]([O:19][CH3:20])=[CH:5][CH:4]=1.[F:21][C:22]1[CH:27]=[CH:26][C:25](B(O)O)=[CH:24][CH:23]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].C(O)C.O.COCCOC>[F:21][C:22]1[CH:27]=[CH:26][C:25]([CH2:2][C:3]2[N:8]=[C:7]([C:9]3[CH:14]=[CH:13][CH:12]=[C:11]([C:15]([F:18])([F:17])[F:16])[CH:10]=3)[C:6]([O:19][CH3:20])=[CH:5][CH:4]=2)=[CH:24][CH:23]=1

Participants

Conditions

Temperature: 80 °C

Procedure

To the 6-bromomethyl-3-methoxy-2-(3-trifluoromethyl-phenyl)-pyridine synthesized above (0.2 g, 0.58 mmol), 4-fluorophenylboronic acid (0.12 g, 0.87 mmol), PPh3 (0.03 g, 0.12 mmol), K3PO4 (0.37 g, 1.73 mmol) and Pd(OAc)2 (0.013 g, 0.058 mmol) was added DME (4.0 mL), and EtOH—H2O (1:1, 1.0 mL). The reaction was stirred at 80° C. for 20 h. The reaction was cooled to room temperature, concentrated. The residue was purified by silica gel column chromatography using 1:1 dichloromethane-hexanes then dichloromethane to afford 0.056 g (22%) of 6-(4-fluoro-benzyl)-3-methoxy-2-(3-trifluoromethyl-phenyl)-pyridine (P-065) as a clear viscous liquid. 1H NMR (CDCl3, 400 MHz): 8.24 (s, 1H), 8.14 (d, J=8.0 Hz, 1H), 7.6-7.64 (m, 1H), 7.52-7.65 (m, 1H), 7.2-7.34 (m, 4H), 6.96-7.05 (m, 2H), 4.14 (s, 2H), 3.85 (s, 3H); MS (APCI+): 362.1 (M+1), LC-MS: 97.2%.

Workup

temperatureThe reaction was cooled to room temperature
concentrationconcentrated
customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record: ord-8cd7513eac954268814bb3e264743679
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08791267B2

Reaction notes

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