Triethylamine → HCID 86762592, compound

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).

1. stirringstirring at 0° C.
2. waitwas continued for 1 h
3. customThe cold reaction mixture
4. customwas transferred into a separatory funnel
5. washwashed with 1 M HCl (400 mL) and 10% brine (400 mL)
6. extractionThe aqueous layers were extracted with dichloromethane (400 mL)
7. dry with materialthe combined organic layers were dried over Na2SO4
8. filtrationFiltration and evaporation of the solvent (35-45° C./≧10 mbar)

ORD record

ord-7bbe1e8eeee348ee971c182e1bf5b4b6

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796471B2