反応 #632017

反応方程式

DBU

product

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

CDI

cyclopropylsulfonamide

→

desired product

収率 92.0%

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

収率 92.0%

溶媒

THF

THF

反応条件

後処理

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

実験手順

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).

出典