1,1-Dichloroethane → HCID 67068806, compound

HRID 553446Notes

Reaction equation

HRID 553446 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].ClC(Cl)C.C(N1C=CN=C1)(N1C=CN=C1)=O.[CH:33]1([S:36]([NH2:39])(=[O:38])=[O:37])[CH2:35][CH2:34]1.C1CCN2C(=NCCC2)CC1>>[C:1]([O:5][C:6]([NH:8][C@:9]1([C:14]([C:33]2([S:36]([NH2:39])(=[O:38])=[O:37])[CH2:35][CH2:34]2)=[O:16])[CH2:11][C@@H:10]1[CH:12]=[CH2:13])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 5

HCID 63651,1-DichloroethaneHCID 682631,1'-CarbonyldiimidazoleHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 15765418CyclopropanesulfonamideHCID 45789195HCID 45789195, compound

Product 1

HCID 67068806HCID 67068806, compoundYield 45%

Conditions

Temperature
50 °C

Procedure

(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.

Workup

  1. stirringStirring
  2. waitwas continued at 50° C. for a further 15 hours by when LCMS analysis of the reaction mixture
  3. customconsumption of the starting material
  4. customThe solvent was removed under vacuum
  5. customThe residue was partitioned between dichloromethane (50 mL) and 0.5 M hydrochloric acid (20 mL)
  6. washThe organic phase was washed with brine (20 mL)
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent removed under vacuum
  10. customThe residue was purified by flash column chromatography
  11. customremoving the solvent under vacuum

Sources & evidence

ORD record
ord-b827143c67b54bcaaaa62f9dc93f04c6
Source dataset
uspto-grants-2011_11
Patent number
US08048862B2

Reaction notes

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