Reaction #502121

Reaction equation

(2S)-2-(6-methoxy(2-naphthyl))propanoic acid

((4S)-2,2,4-trimethyl-1,3-dioxolan-4-yl)methan-l-ol

→

title compound

Yield 96.5%

((4R)-2,2,4-Trimethyl-1,3-dioxolan-4-yl)methyl(2S)-2-(6-methoxy(2-naphthyl))propanoate

Yield 96.5%

Solvents

dichloromethane

Conditions

Workup

1. 1
   Otherquenched with water
2. 2
   WashThe organic layer was washed with brine
3. 3
   Dryingdried over sodium sulfate
4. 4
   Filtrationfiltered
5. 5
   Othersolvent was evaporated under reduced pressure
6. 6
   OtherThe product was purified by column chromatography over silica gel eluting with 20% ethyl acetate in hexane

Procedure

To a solution of (2S)-2-(6-methoxy(2-naphthyl))propanoic acid (naproxen, 32.2 g, 0.14 mol) and ((4S)-2,2,4-trimethyl-1,3-dioxolan-4-yl)methan-l-ol (15 g, 0.113 mol) in anhydrous dichloromethane (750 mL) were added 1-ethyl-3-(3-dimethylaminopropyl)carbamide hydrochloride (EDAC) (23 g, 0.12 mol) and N,N-dimethylaminopyridine (DMAP, 7.5 g, 61 mmol) at room temperature under nitrogen atmosphere. The reaction mixture was stirred at room temperature overnight, then quenched with water. The organic layer was washed with brine, dried over sodium sulfate, filtered, and solvent was evaporated under reduced pressure. The product was purified by column chromatography over silica gel eluting with 20% ethyl acetate in hexane to give the title compound (37.5 g, 96.5% yield) as a white solid, mp 65-66° C. 1H NMR (CDCl3) δ7.75 (d, J=8.7 Hz, 1H), 7.73 (d, J=1.2 Hz, 1H), 7.46 (dd, J=8.4 and 1.7 Hz, 1H), 7.15 (m, 2H), 4.27 (m, 1H), 4.19 (m, 2H), 4.03-3.92 (m, 2H), 3.96 (s, H), 3.69 (dd, J=8.4 and 6.0 Hz, 1H), 1.64 (d, J=7.1 Hz, 3H), 1.40 (s, 3H), 1.37 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 174.4, 157.6, 135.3, 133.7, 129.2, 128.8, 127.1, 126.1, 125.9, 119.0, 109.7, 105.5, 73.4, 66.2, 64.8, 55.2, 45.2, 26.5, 25.3, 18.4; LRMS (APIMS) m/z 362 (M+NH4)+.

Source