Reacción #1884973

Ecuación de reacción

DBU

product

1(R)-tert-butoxycarbonylamino-2(S)-vinyl-cyclopropanecarboxylic acid

CDI

cyclopropylsulfonamide

→

title compound

Rendimiento 92.0%

cyclopropanesulfonic acid (1-(R)-tert-butoxycarbonylamino-2-(S)-vinylcyclopropanecarbonyl)-amide

Rendimiento 92.0%

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturaat reflux for 50 minutes under nitrogen
2. 2
   OtroThe mixture was quenched with 1N HCl to pH 1 and THF
3. 3
   Concentraciónwas concentrated in vacuo
4. 4
   ExtracciónThe suspension was extracted with ethyl acetate (2×50 mL)
5. 5
   Secadothe combined organic extracts were dried (Na2SO4)
6. 6
   Filtraciónfiltered
7. 7
   Concentraciónconcentrated
8. 8
   OtroPurification
9. 9
   Otroby recrystallization from hexanes-ethyl acetate (1:1)

Procedimiento

A solution of the product of Step 1 (2.62 g, 11.5 mmol) and CDI (2.43 g, 15.0 mmol) in THF (40 mL) was heated at reflux for 50 minutes under nitrogen. The solution was cooled to room temperature and transferred by cannula to a solution of cyclopropylsulfonamide (1.82 g, 15.0 mmol) in THF (10 mL). To the resulting solution was added DBU (2.40 mL, 16.1 mmol) and stirring was continued for 20 hours. The mixture was quenched with 1N HCl to pH 1 and THF was concentrated in vacuo. The suspension was extracted with ethyl acetate (2×50 mL) and the combined organic extracts were dried (Na2SO4), filtered, and concentrated. Purification by recrystallization from hexanes-ethyl acetate (1:1) afforded the title compound (2.4 g) as a white solid. The mother liquor was purified by a Biotage 40S column (eluted 9% acetone in dichloromethane) to give a second batch of the title compound (1.1 g). Both batches were combined (total yield 92%). 1H NMR (DMSO-d6) δ 0.96-1.10 (m, 4H), 1.22 (dd, J=5.5, 9.5 Hz, 1H), 1.39 (s, 9H), 1.70 (t, J=5.5 Hz, 1H), 2.19-2.24 (m, 1H), 2.90 (m, 1H), 5.08 (d, J=10 Hz, 1H), 5.23 (d, J=17 Hz, 1H), 5.45 (m, 1H), 6.85, 7.22 (s, NH (rotamers); MS m/z 331 (M++H).

Fuente