Hydrochloric Acid → ethyl (1S,2R)-1-amino-2-vinyl-cyclopropanecarboxylate;hydrochloride

Temperature

0 °C

To a solution of potassium tert-butoxide (11.55 g, 102.9 mmol) in THF (450 mL) at −78° C. was added the commercially available N,N-dibenzyl imine of glycine ethyl ester (25.0 g, 93.53 mmol) in THF (112 mL). The reaction mixture was warmed to 0° C., stirred for 40 min, and was then cooled back to −78° C. To this solution was added trans-1,4-dibromo-2-butene (20.0 g, 93.50 mmol), the mixture stirred for 1 h at 0° C. and was cooled back to −78° C. Potassium tert-butoxide (11.55 g, 102.9 mmol) was added, the mixture immediately warmed to 0° C., and was stirred one more hour before concentrating in vacuo. The crude product was taken up in Et2O (530 mL), 1N aq. HCl solution (106 mL, 106 mmol) added and the resulting biphasic mixture stirred for 3.5 h at rt. The layers were separated and the aqueous layer was washed with Et2O (2×) and basified with a saturated aq. NaHCO3 solution. The desired amine was extracted with Et2O (3×) and the combined organic extract was washed with brine, dried (MgSO4), and concentrated in vacuo to obtain the free amine. This material was treated with a 4N HCl solution in dioxane (100 mL, 400 mmol) and concentrated to afford (1R,2S)/(1S,2R)-1-amino-2-vinylcyclopropane carboxylic acid ethyl ester hydrochloride as a brown semisolid (5.3 g, 34% yield) identical to the material obtained from procedure A, except for the presence of a small unidentified aromatic impurity (8%).

1. temperaturewas then cooled back to −78° C
2. stirringthe mixture stirred for 1 h at 0° C.
3. temperaturewas cooled back to −78° C
4. temperaturethe mixture immediately warmed to 0° C.
5. stirringwas stirred one more hour
6. concentrationbefore concentrating in vacuo
7. stirringthe resulting biphasic mixture stirred for 3.5 h at rt
8. customThe layers were separated
9. washthe aqueous layer was washed with Et2O (2×)
10. extractionThe desired amine was extracted with Et2O (3×)
11. extractionthe combined organic extract
12. washwas washed with brine
13. dry with materialdried (MgSO4)
14. concentrationconcentrated in vacuo

ORD record

ord-73c632be8e1042748e774289a963c2d9

Source dataset

uspto-grants-2006_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07132504B2