Potassium Phosphate, Tribasic → Methyl 6-(adamantan-1-ylmethoxy)-5-cyclopropylnicotinate

A mixture of methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinate (1.29 g, 3.84 mmol), cyclopropylboronic acid (0.43 g, 4.99 mmol), potassium phosphate (3.26 g, 15.40 mmol), tricyclohexylphosphine tetrafluoroborate (0.14 g, 0.38 mmol) and palladium acetate (0.04 g, 0.19 mmol) in degassed toluene (50 mL) and degassed water (5 mL) was refluxed under nitrogen for 7 h. The reaction mixture was cooled to ambient temperature and diluted with ethyl acetate (100 mL), washed with water (50 mL), saturated ammonium chloride (50 mL) and brine (50 mL); dried over anhydrous sodium sulfate, filtered through diatomaceous earth and concentrated in vacuo. The residue was purified by flash chromatography eluting with 5% ethyl acetate in hexanes to afford the title compound as a white solid (1.17 g, 89%); 1H NMR (300 MHz, CDCl3) δ 8.57 (d, J=2.2 Hz, 1H), 7.67 (d, J=2.2 Hz, 1H), 3.95 (s, 2H), 3.85 (s, 3H), 2.09-1.96 (m, 4H), 1.78-1.63 (m, 12H), 0.99-0.91 (m, 2H), 0.72-0.65 (m, 2H); MS (ES+) m/z: 342.22 (M+1).

1. customdegassed water (5 mL)
2. temperaturewas refluxed under nitrogen for 7 h
3. additiondiluted with ethyl acetate (100 mL)
4. washwashed with water (50 mL), saturated ammonium chloride (50 mL) and brine (50 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered through diatomaceous earth
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography
9. washeluting with 5% ethyl acetate in hexanes

ORD record

ord-4d039d9b3bf44f8587cd653f1bfc61d1

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933236B2