Hydrochloric Acid → HCID 9990731, compound

The product from Example 1B (4.50 g, 29.2 mmol), and 1,1′-carbonyldiimidazole (5.0 g, 30.8 mmol, 1.06 equiv) were combined in 1,2-dimethoxyethane (50 mL) and stirred at room temperature for 1.5 hours. Glycine methyl ester hydrochloride (3.85 g, 30.8 mmol, 1.06 equiv, purchased from Aldrich) and water (0.2 mL) were added and the reaction mixture was heated at 65° C. for 6 hours. The reaction solution was cooled to room temperature, diluted with ethyl acetate (250 mL) and washed water (2×100 mL). The organic extract was concentrated and the residue was dissolved in ethanol (20 mL). An aqueous solution of NaOH (1.52 g, 38 mmol, 1.3 equiv) was added and the mixture was agitated at room temperature for 1 hour. The reaction mixture was diluted with ethyl acetate (250 mL) and water (100 mL), which was acidified with to pH 3 by the addition of concentrated HCl. The organic extract was concentrated and the residue was crystallized from ethyl acetate (40 mL) to afford the title compound (4.0 g, 65%). 1H NMR (CDCl3, 400 MHz) δ 6.30 (m, 1H), 4.10 (d, 2H), 1.25-1.7 (m, 11H), 1.16 (dd, 1H), 0.81 (dd, 1H); MS, m/z, 212 (M+H)+.

1. temperaturethe reaction mixture was heated at 65° C. for 6 hours
2. temperatureThe reaction solution was cooled to room temperature
3. washwashed water (2×100 mL)
4. extractionThe organic extract
5. concentrationwas concentrated
6. dissolutionthe residue was dissolved in ethanol (20 mL)
7. stirringthe mixture was agitated at room temperature for 1 hour
8. extractionThe organic extract
9. concentrationwas concentrated
10. customthe residue was crystallized from ethyl acetate (40 mL)

ORD record

ord-4d6348aa65db47b29daefbbeacd64b5b

Source dataset

uspto-grants-2011_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07932245B2