Реакция #1884973

Уравнение реакции

DBU

product

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

CDI

cyclopropylsulfonamide

→

title compound

Выход 92.0%

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

Выход 92.0%

Растворители

THF

THF

Условия реакции

Обработка

1. 1
   Температураat reflux for 50 minutes under nitrogen
2. 2
   ДругоеThe mixture was quenched with 1N HCl to pH 1 and THF
3. 3
   Концентрированиеwas concentrated in vacuo
4. 4
   ЭкстракцияThe suspension was extracted with ethyl acetate (2×50 mL)
5. 5
   Сушкаthe combined organic extracts were dried (Na2SO4)
6. 6
   Фильтрацияfiltered
7. 7
   Концентрированиеconcentrated
8. 8
   ДругоеPurification
9. 9
   Другоеby recrystallization from hexanes-ethyl acetate (1:1)

Методика

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).

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