Methanol → Methyl 5-chloro-2-fluoro-4-((3-(hydroxymethyl)-adamantan-1-yl)methoxy)benzoate

A solution of 5-chloro-2-fluoro-4-((3-(hydroxymethyl)adamantan-1-yl)methoxy)benzoic acid (3.53 g, 9.57 mmol), 4-dimethylaminopyridine (0.23 g, 1.90 mmol), and methanol (3.87 mL, 95.70 mmol) in anhydrous dimethylformamide (50 mL) under nitrogen was treated with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (3.67 g, 19.10 mmol). The reaction mixture was stirred for 24 hours at ambient temperature; diluted with ethyl acetate (200 mL) and washed with water (100 mL), saturated ammonium chloride (100 mL), and brine (100 mL); dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography (3:1 hexanes:ethyl acetate) to provide the title compound (0.65 g, 18%): 1H NMR (300 MHz, CDCl3) δ 7.90 (d, J=7.9 Hz, 1H), 6.59 (d, J=12.6 Hz, 1H), 3.85 (s, 3H), 3.56 (s, 2H), 3.23 (s, 2H), 2.11 (br s, 1H), 1.74-1.40 (m, 14H); MS (ES+) m/z 383.1, 385.1 (M+1).

1. washwashed with water (100 mL), saturated ammonium chloride (100 mL), and brine (100 mL)
2. dry with materialdried over anhydrous sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated in vacuo
5. customThe residue was purified by silica gel column chromatography (3:1 hexanes:ethyl acetate)

ORD record

ord-9bd29afc9b2146019b342876c685aed9

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08952169B2