Chloride → HCID 21341527, compound

Participants

Reaction Steps

This transformation was done in three steps without characterizing the individual intermediates. Mesyl chloride (921 μl, 5 eq.) and triethylamine (1.66 mL, 5 eq.) were quickly added to a solution of N-(tert-butoxycarbonyl)-trans-4-(2-hydroxyethoxy)-L-proline ethyl ester (721 mg, 2.4 mmol) in dichloromethane (25 mL) at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at that temperature for 1 hour, diluted in dichloromethane, washed twice with 1 N HCl, twice with sat NaHCO3, twice with brine, dried (Na2SO4) and concentrated. The crude residue (0.9 g) was dissolved in dimethylformamide (25 mL) and sodium azide (2.48 g, 16 eq.) and anunonium chloride (1.27 g, 10 eq.) were added. The reaction mixture was stirred at 90° C. for 16 h. after which it was cooled and concentrated under reduced pressure and the residue partitioned between dichloromethane and water. The aqueous layer was extracted twice with dichloromethane and the combined organic layers were washed twice with water, twice with brine, dried (Na2SO4) and concentrated. The crude residue (0.76 g) was dissolved in anhydrous tetrrhydrofuran (10 mL) and dry tin chloride (661 mg, 1.5 eq.), thiophenol (1.43 mL, 6 eq.) and triethylamine (4.5 eq.) were added. The reaction mixture was stirred at 25° C. for Ihour, then poured into ethyl acetate and washed with 1 N HCl, 1 N NaOH, brine, dried (Na2SO4) and concentrated. The product (668 mg, 92%) was used crude: 1H NMR (300 MHz, CDCl3) δ 1.39 (m, 3H), 1.53, 1.58 (2s, 9H), 2.16 (m, 1H), 2.43 (m, 1H), 2.95 (m, 2H), 3.57 (m, 2H), 3.69 (m, 2H), 4.18 (m, 1H), 4.24 (m, 2H), 4.40 (m, 1H).

Provenance & Evidence