Methanol → Methyl 6-(adamantan-1-ylmethoxy)-5-chloronicotinate

A solution of 6-(adamantan-1-ylmethoxy)-5-chloronicotinic acid (4.20 g, 13.10 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide (5.00 g, 26.10 mmol), triethylamine (3.6 mL, 26.10 mmol) and methanol (1.05 mL, 26.10 mmol) in methylene chloride (100 mL) was stirred under nitrogen for 18 h. The reaction mixture was concentrated in vacuo and the residue was dissolved in ethyl acetate (300 mL). The mixture was washed with a 1:1(v/v) mixture of 1 M aqueous hydrochloric acid/brine (2×100 mL), brine (2×100 mL); dried over anhydrous sodium sulfate; filtered and concentrated in vacuo. The residue was purified by flash chromatography eluting with 10% ethyl acetate in hexanes to afford the title compound as a white solid (1.90 g, 43%); 1H NMR (300 MHz, CDCl3) δ 8.66-8.62 (m, 1H), 8.19-8.16 (m, 1H), 3.99 (s, 2H), 3.89 (s, 3H), 2.04-1.96 (m, 3H), 1.78-1.62 (m, 12H).

1. concentrationThe reaction mixture was concentrated in vacuo
2. dissolutionthe residue was dissolved in ethyl acetate (300 mL)
3. washThe mixture was washed with a 1:1(v/v)
4. additionmixture of 1 M aqueous hydrochloric acid/brine (2×100 mL), brine (2×100 mL)
5. dry with materialdried over anhydrous sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography
9. washeluting with 10% ethyl acetate in hexanes

ORD record

ord-20470fe56c3b4b74b1d2485e61ffd421

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08933236B2