Triethylamine → HCID 86762592, compound

Participants

Reaction Steps

To a suspension of hydroxyproline methyl ester hydrochloride (36.3 g, 200 mol), triethylamine (65.8 g, 650 mmol) and dimethylaminopyridine (1.25 g, 10 mmol) in dichloromethane (800 mL) was added at 0° C. the 1-methyl-cyclopropanecarbonyl chloride (24.9 g, 210 mmol) over 0.5 h. After additional stirring for 2 h, methanesulfonyl chloride (28.64 g, 250 mmol; note 7) was added over 0.5 h and stirring at 0° C. was continued for 1 h. The cold reaction mixture was transferred into a separatory funnel and washed with 1 M HCl (400 mL) and 10% brine (400 mL). The aqueous layers were extracted with dichloromethane (400 mL) and the combined organic layers were dried over Na2SO4. Filtration and evaporation of the solvent (35-45° C./≧10 mbar) afforded crude, crystalline product (63.8 g) which was dissolved in isobutyl acetate (250 mL) at ˜70° C. After seeding at ˜50° C., crystallization was completed by cooling to room temperature and stirring at −20° C. overnight. Filtration and washing with cold isobutyl acetate gave after drying (50° C./10 mbar/3 h) the title product (57.5 g, 94.2%) as a white, crystalline powder, mp. 102-103° C. [α]D20=−10.3 (c 1.0; CHCl3). 1H NMR (CDCl3, 400 MHz) δ 0.50-0.70 (m, 2H), 0.90 (m, 1H), 1.10 (m, 1H), 1.34 (s, 3H), 2.23 (m, 1H), 2.59 (m, 1H), 3.06 (s, 3H), 3.74 (s, 3H), 3.95 (d, 1H), 4.25 (d, 1H), 4.63 (br t, 1H), 5.35 (s, 1H).

Provenance & Evidence