反应 #632017

反应方程式

DBU

product

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

CDI

cyclopropylsulfonamide

→

desired product

收率 92.0%

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

收率 92.0%

溶剂

THF

THF

反应条件

后处理

1. 1
   温度to reflux for 50 minutes under nitrogen
2. 2
   其他The mixture was quenched with 1N HCl to pH 1 and THF
3. 3
   浓缩was concentrated in vacuo
4. 4
   萃取The suspension was extracted with ethyl acetate (2×50 mL)
5. 5
   干燥the combined organic extracts were dried (Na2SO4)
6. 6
   过滤filtered
7. 7
   浓缩concentrated
8. 8
   其他Purification by recystallization from hexanes-ethyl acetate (1:1)

实验过程

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 to 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 recystallization from hexanes-ethyl acetate (1:1) provided the desired product (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 desired product (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); LC-MS (retention time: 1.70 minutes, method B), MS m/z 331 (M++H).

来源