반응 #640628

반응 방정식

Cyclopropanesulfonamide

DBU

(1R,2R)-1-(tert-Butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylic acid

dichloroethane

1,1′-Carbonyldiimidazole

→

title compound

수율 45.0%

(1R,2R)-1-(tert-butoxycarbonylamino)-2-vinyl-cyclopropane-1-carbonyl-cyclopropanesulfonamide

수율 45.0%

반응 조건

후처리

1. 1
   workup.STIRRINGStirring
2. 2
   workup.WAITwas continued at 50° C. for a further 15 hours by when LCMS analysis of the reaction mixture
3. 3
   기타consumption of the starting material
4. 4
   기타The solvent was removed under vacuum
5. 5
   기타The residue was partitioned between dichloromethane (50 mL) and 0.5 M hydrochloric acid (20 mL)
6. 6
   세척The organic phase was washed with brine (20 mL)
7. 7
   건조dried over sodium sulfate
8. 8
   여과filtered
9. 9
   기타the solvent removed under vacuum
10. 10
    기타The residue was purified by flash column chromatography
11. 11
    기타removing the solvent under vacuum

실험 절차

(1R,2R)-1-(tert-Butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylic acid (1.72 g, 7.57 mmol., 1.0 eq.) and dichloroethane (38 mL) were charged into a 100 mL round bottom flask. 1,1′-Carbonyldiimidazole (1.72 g, 10.61 mmol., 1.4 eq.) was added portionwise and the reaction mixture stirred at 50° C. for 15 hours. Cyclopropanesulfonamide (2.47 g, 20.4 mmol., 2.7 eq.) was added portionwise followed by dropwise addition of DBU (3.11 g, 20.4 mmol., 2.7 eq.). Stirring was continued at 50° C. for a further 15 hours by when LCMS analysis of the reaction mixture showed full consumption of the starting material. The solvent was removed under vacuum. The residue was partitioned between dichloromethane (50 mL) and 0.5 M hydrochloric acid (20 mL). The organic phase was washed with brine (20 mL), dried over sodium sulfate, filtered and the solvent removed under vacuum. The residue was purified by flash column chromatography using heptanes:ethyl acetate gradient (60:50 to 50:50) as eluent. After combining the relevant fractions and removing the solvent under vacuum, 1.12 g (45%) of the title compound was isolated as a yellow semi solid. 1H NMR (500 MHz, CDCl3) δ ppm 9.71 (br. s, 1 H), 5.61 (br. s, 1 H), 5.32 (d, J=16.87 Hz, 1 H), 5.20-5.28 (m, 1 H), 5.18 (d, J=10.27 Hz, 1 H), 2.88-3.00 (m, 1 H), 2.16 (q, J=8.44 Hz, 1 H), 1.87-1.96 (m, 1 H), 1.51 (s, 9 H), 1.40-1.47 (m, 1 H), 1.24-1.36 (m, 2 H), 1.07-1.16 (m, 1 H), 0.99-1.07 (m, 1 H). LC-MS: purity 100% (ELS), tR 1.74 min, m/z [M−H]-329.10.

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