Acetyl chloride → Methyl 3-amino-3-(3-cyclopentyloxy-4-methoxy-phenyl)propionate

Participants

Reaction Steps

To a stirred suspension of 3-amino-3-(3'-cyclopentyloxy-4'-methoxyphenyl)propionic acid (30 grams, 279 mmol) in methanol (150 mL) at 0° C., was added acetyl chloride (15.2 mL, 212 mmol) dropwise. After 15 minutes, the ice-water bath was removed. The resulting clear solution was stirred at room temperature for 2 h. The system was opened and the solvent was blown off with N2 overnight. To the solid was added methanol (50 mL) and ether (300 mL). The resulting suspension was stirred at room temperature for 1 h. The suspension was filtered and the solid was washed with ether (100 mL). The solid was dissolved in a mixture of aqueous sodium carbonate (200 mL, sat), water (200 mL), and methylene chloride (250 mL). The organic layer was separated. The aqueous layer was extracted with methylene chloride (3×250 mL). The combined organic layers were dried over magnesium sulfate. Removal of solvent gave methyl 3-amino-3-(3'-cyclopentoxy-4'-methoxyphenyl)propionate as an oil (28.41 grams, 90% yield): 1H NMR (CDCl3)δ1.56-1.97 (m, 10H, NH2, C5H8), 2.62 (d, J=7 Hz, 2H, CH2), 3.67 (s, 3H, CH3), 3.81 (s, 3H, CH3), 4.34 (t, J=6.8 Hz, 1H, CH), 4.74-4.79 (dd, J=5, 8.5 Hz, 1H, NCH), 6.78-6.90 (m, 3H, Ar); 13C NMR (CDCl3)δ23.97, 32.76, 44.17, 51.58, 52.25, 56.07, 80.37, 111.96, 113.08, 119.08, 137.25, 147.72, 149.27, 172.49.

Provenance & Evidence