Reaction #632017

Reaction equation

DBU

product

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

CDI

cyclopropylsulfonamide

→

desired product

Yield 92.0%

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

Yield 92.0%

Solvents

THF

THF

Conditions

Workup

1. 1
   Temperatureto reflux for 50 minutes under nitrogen
2. 2
   OtherThe mixture was quenched with 1N HCl to pH 1 and THF
3. 3
   Concentrationwas concentrated in vacuo
4. 4
   ExtractionThe suspension was extracted with ethyl acetate (2×50 mL)
5. 5
   Dryingthe combined organic extracts were dried (Na2SO4)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated
8. 8
   OtherPurification by recystallization from hexanes-ethyl acetate (1:1)

Procedure

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).

Source