4-Methylmorpholine → N-Tiglylglycine methyl ester

Temperature

-15 °C

(E)-2-methyl-2-butenoic acid (300 mg, 3.00 mmol) was dissolved in CH2Cl2 (6 mL) and N-methyl morpholine (396 μL, 3.60 mmol) was added to the solution. The reaction mixture was cooled to −15° C. Isobutyl chloroformate (389 μL, 3.00 mmol) was added and stirred at −15° C. for 15 min. Glycine methyl ester hydrochloride (377 mg, 3.00 mmol), CH2Cl2 (4 mL), and N-methyl morpholine (330 μL, 3.00 mmol) were added to the solution. After stirring at −15° C. for 15 min, the reaction mixture was warmed to 24° C. and stirred for 16 h. CH2Cl2 (60 mL) was added to the reaction mixture and the organic layer was washed with 1 N aq HCl (3×20 mL) and 5% aq NaHCO3 (3×20 mL). The organic layer was dried over anhydrous Na2SO4 and the solvent was evaporated. The crude product was purified by silica gel column chromatography using 30% and 40% EtOAc/CH2Cl2 to give 11 (219 mg, 43% yield). 1H-NMR (400 MHz, CDCl3) δ 6.47 (m, 1H), 6.37 (bs, 1H), 4.05 (d, J=4.8 Hz, 2H), 3.73 (s, 3H), 1.83 (m, 3H), 1.73 (m, 3H); 13C-NMR (100 MHz, CDCl3) δ 170.8, 169.4, 131.8, 131.2, 52.4, 41.6, 14.0, 12.3; HRMS (ESI) calcd for C8H14NO3 [M+H]+172.0974, found 172.0974.

1. stirringAfter stirring at −15° C. for 15 min
2. temperaturethe reaction mixture was warmed to 24° C.
3. stirringstirred for 16 h
4. washthe organic layer was washed with 1 N aq HCl (3×20 mL) and 5% aq NaHCO3 (3×20 mL)
5. dry with materialThe organic layer was dried over anhydrous Na2SO4
6. customthe solvent was evaporated
7. customThe crude product was purified by silica gel column chromatography

ORD record

ord-a188c69f0c404b528239b2c982bfc844

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08232360B2