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

HRID 553447Notes

Reaction equation

HRID 553447 reaction equation
[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([OH:16])=O)[CH2:11][C@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:17](N1C=CN=C1)([N:19]1[CH:23]=CN=C1)=O.C[NH:30][S:31](NC)(=[O:33])=[O:32].C1CCN2C(=NCCC2)CC1>ClC(Cl)C>[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([NH:30][S:31]([N:19]([CH3:23])[CH3:17])(=[O:33])=[O:32])=[O:16])[CH2:11][C@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 89736N,N'-DimethylsulfamideHCID 10376443(1R,2S)-1-(((1,1-Dimethylethoxy)carbonyl)amino)-2-ethenylcyclopropanecarboxylic acid

Product 1

HCID 59645136(1R,2S)-1-(tert-Butoxycarbonylamino)-2-vinyl-cyclopropane-1-carbonyl-N,N-dimethylsulfamideYield 78.7%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

(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.

Workup

  1. filtrationThe molecular sieves were filtered off
  2. washwashed with dichloroethane (2×5 mL)
  3. stirringthe reaction mixture stirred vigorously at 50° C. for 1 hour until no more gas evolution
  4. stirringStirring
  5. waitwas continued at 50° C. for a further 15 hours by which time LCMS analysis of the reaction mixture
  6. customconsumption of the starting material
  7. washThe reaction mixture was washed with 0.5 M hydrochloric acid (3×50 mL) and brine (50 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. customThe residue was purified by flash column chromatography
  11. customthe relevant fractions and solvent removal

Sources & evidence

ORD record
ord-4285c7377a89414ea038994afe4de543
Source dataset
uspto-grants-2011_11
Patent number
US08048862B2

Reaction notes

Loading…