Potassium Phosphate, Tribasic → Methyl 4-(5-fluoro-2-methoxypyridin-4-yl)-3-(1-vinylcyclopentyl)benzoate

HRID 404390

Reaction equation

FC(F)(F)S(O[C:7]1[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][C:8]=1[C:17]1([CH:22]=[CH2:23])[CH2:21][CH2:20][CH2:19][CH2:18]1)(=O)=O.[F:26][C:27]1[C:28](B(O)O)=[CH:29][C:30]([O:33][CH3:34])=[N:31][CH:32]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1>CN(C=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:26][C:27]1[C:28]([C:7]2[CH:16]=[CH:15][C:10]([C:11]([O:13][CH3:14])=[O:12])=[CH:9][C:8]=2[C:17]2([CH:22]=[CH2:23])[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:29][C:30]([O:33][CH3:34])=[N:31][CH:32]=1

Participants

Conditions

Temperature: 90 °C

Procedure

The reaction mixture of methyl 4-(trifluoromethylsulfonyloxy)-3-(1-vinylcyclopentyl)benzoate 26.4 (0.29 g, 0.8 mmol), 5-fluoro-2-methoxypyridin-4-ylboronic acid (0.2 g, 1.0 mmol) (commercially available from Sigma-Aldrich, St. Louis, Mo., USA), potassium phosphate (0.5 g, 2.0 mmol), S-phos (0.06 g, 0.2 mmol) and palladium acetate (0.02 g, 0.08 mmol) in DMF (1.5 mL) was purged with nitrogen three times. The resulting mixture was heated at 90° C. for 2 hours. After work up, the product was purified by CombiFlash® silica gel column chromatography, eluting with hexane/EtOAc 9/1, to give the compound 26.5. 1H NMR (500 MHz, CDCl3) δ ppm 8.20 (1H, d, J=1.7 Hz), 8.00 (1H, s), 7.91 (1H, dd, J=7.8, 1.7 Hz), 7.10 (1H, d, J=8.1 Hz), 6.63 (1H, d, J=4.9 Hz), 5.87 (1H, dd, J=17.4, 10.5 Hz), 4.97 (1H, d, J=10.5 Hz), 4.69 (1H, d, J=17.4 Hz), 3.98 (3H, s), 3.85 (3H, s), 2.00-2.20 (1H, m), 1.80-1.96 (1H, m), 1.51-1.75 (6H, m). MS ESI (pos.) m/e: 355.9 (M+H)+.

Workup

customAfter work up, the product was purified by CombiFlash® silica gel column chromatography
washeluting with hexane/EtOAc 9/1

Sources & evidence

ORD record: ord-8297b3d3fc01485a872ffe4eeb20a885
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748462B2

Linked notes

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