Triethylamine → 1-(4-Methyl-1,2,3,4-tetrahydroquinoxaline-1-carbonyl)cyclopropanecarboxylic acid

To a solution of cyclopropane-1,1-dicarboxylic acid (1 g, 7.69 mmol) in dry tetrahydrofuran (20 mL) at 0° C. under nitrogen, was added triethylamine (1.07 mL, 7.69 mmol) and the mixture was stirred for 30 min. Thionyl chloride (0.56 mL, 7.69 mmol) was added, stirring was continued at 0° C. for 30 min., 1-methyl-1,2,3,4-tetrahydroquinoxaline (310) (1.2 g, 8.46 mmol)[Smith R. F. et al., J. Org. Chem., 24, 1959, 205] was added and the reaction mixture was allowed to warm to room temperature. After stirring for 1 h, ethyl acetate was added and the resulting mixture was extracted twice with a 1N NaOH solution. The combined aqueous layers were acidified to pH 4-5 by addition of a 3N HCl solution and extracted 4 times with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The residue was purified by Biotage (Si 12M, gradient: MeOH in dichloromethane 0% to 10%) to afford title compound 311 (638 mg, 32% yield). MS (m/z): 259.0 (M−H).

1. stirringstirring
2. waitwas continued at 0° C. for 30 min.
3. stirringAfter stirring for 1 h
4. extractionthe resulting mixture was extracted twice with a 1N NaOH solution
5. additionThe combined aqueous layers were acidified to pH 4-5 by addition of a 3N HCl solution
6. extractionextracted 4 times with ethyl acetate
7. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
8. customthe solvent was removed under reduced pressure
9. customThe residue was purified by Biotage (Si 12M, gradient: MeOH in dichloromethane 0% to 10%)

ORD record

ord-19e3392dfb204c63ba96882ee8bd3f26

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08093264B2