반응 #640629

반응 방정식

DBU

1,1′-Carbonyldiimidazole

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

Dimethylsulfamide

→

(1R,2S)-1-(tert-Butoxycarbonylamino)-2-vinyl-cyclopropane-1-carbonyl-N,N-dimethylsulfamide

수율 78.7%

용매

dichloroethane

반응 조건

후처리

1. 1
   여과The molecular sieves were filtered off
2. 2
   세척washed with dichloroethane (2×5 mL)
3. 3
   workup.STIRRINGthe reaction mixture stirred vigorously at 50° C. for 1 hour until no more gas evolution
4. 4
   workup.STIRRINGStirring
5. 5
   workup.WAITwas continued at 50° C. for a further 15 hours by which time LCMS analysis of the reaction mixture
6. 6
   기타consumption of the starting material
7. 7
   세척The reaction mixture was washed with 0.5 M hydrochloric acid (3×50 mL) and brine (50 mL)
8. 8
   건조dried over sodium sulfate
9. 9
   여과filtered
10. 10
    기타The residue was purified by flash column chromatography
11. 11
    기타the relevant fractions and solvent removal

실험 절차

(1R,2S)-1-(tert-Butoxycarbonylamino)-2-vinyl-cyclopropane-1-carboxylic acid (1.3 g, 5.72 mmol, 1.0 eq.), dichloroethane (30 mL) and molecular sieves were charged into a 100 mL round bottom flask. The mixture was stirred at room temperature for 15 minutes. The molecular sieves were filtered off and washed with dichloroethane (2×5 mL). 1,1′-Carbonyldiimidazole (1.29 g, 8.01 mmol, 1.4 eq.) was added portionwise and the reaction mixture stirred vigorously at 50° C. for 1 hour until no more gas evolution was noticed. Dimethylsulfamide (1.70 g, 13.62 mmol, 1.7 eq.) was added portionwise followed by dropwise addition of DBU (3.2 mL, 21.63 mmol, 2.7 eq.). Stirring was continued at 50° C. for a further 15 hours by which time LCMS analysis of the reaction mixture showed full consumption of the starting material. The reaction mixture was washed with 0.5 M hydrochloric acid (3×50 mL) and brine (50 mL), dried over sodium sulfate and filtered. The residue was purified by flash column chromatography, using a methanol:dichloromethane gradient (from neat dichloromethane to 2% methanol in dichloromethane). After combining the relevant fractions and solvent removal, 1.5 g (78%) of (1R,2S)-1-(tert-Butoxycarbonylamino)-2-vinyl-cyclopropane-1-carbonyl-N,N-dimethylsulfamide was isolated as a white solid. 1H NMR (500 MHz, CDCl3) δ ppm 8.90-9.88 (m, 1 H) 5.46-5.73 (m, 2 H) 5.14 (d, J=10.38 Hz, 1 H) 2.90 (s, 6 H) 2.12 (q, J=8.70 Hz, 1 H) 1.87 (dd, J=7.93, 5.80 Hz, 1 H) 1.45 (br. s, 9 H) 1.23-1.38 (m, 1 H). LC-MS: purity 99% (UV), m/z [M+Na]+ 356.35.

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