Bromochloromethane → Chloromethyl 6-(2-chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoate

HRID 2357754Notes

Reaction equation

HRID 2357754 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][CH2:9][C:10]2[O:11][CH:12]=[CH:13][CH:14]=2)[C:5]([C:15]([O:17][CH2:18][C:19]([Cl:22])([Cl:21])[Cl:20])=[O:16])=[CH:4][C:3]=1[S:23]([NH:26][CH2:27][O:28][C:29](=[O:37])[CH2:30][CH2:31][CH2:32][CH2:33][C:34]([OH:36])=[O:35])(=[O:25])=[O:24].C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:45][Cl:46]>CO.O>[Cl:1][C:2]1[CH:7]=[C:6]([NH:8][CH2:9][C:10]2[O:11][CH:12]=[CH:13][CH:14]=2)[C:5]([C:15]([O:17][CH2:18][C:19]([Cl:22])([Cl:21])[Cl:20])=[O:16])=[CH:4][C:3]=1[S:23]([NH:26][CH2:27][O:28][C:29](=[O:37])[CH2:30][CH2:31][CH2:32][CH2:33][C:34]([O:36][CH2:45][Cl:46])=[O:35])(=[O:25])=[O:24]

Participants

5

Reactant 3

HCID 6333BromochloromethaneHCID 10796Cesium carbonateHCID 684556356-(2-Chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoic acid

Product 1

HCID 68454251Chloromethyl 6-(2-chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoate

Reagents, catalysts & solvents 1

HCID 22242641Methanol--water (1/1)Solvent

Procedure

The 6-(2-chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoic acid (0.060 mole) is dispersed with stirring in a methanol-water mixture (100 mL), and an aqueous solution of cesium carbonate (2 molar) is added dropwise until the solution pH is 6.6. The volatiles are removed by spin evaporation in vacuo. The resulting cesium salt is dried by addition of toluene and removal of the volatiles under reduced pressure. This is repeated several times. The dry cesium salt is dissolved in dimethylformamide (100 mL), and bromochloromethane (Aldrich) (0.060 mole) is slowly added to the solution. The reaction is stirred at ambient temperature in the dark for 12 hours. The mixture is filtered to remove cesium bromide, and the volatiles are removed by spin evaporation in vacuo. The reaction mixture is diluted with dichloromethane (200 mL) and extracted with sodium bicarbonate solution, washed with water, and then with a saturated sodium chloride solution. The organic layer may be dried over sodium sulfate, filtered and concentrated in vacuo to give crude product, which may be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent. The fractions that contain pure product may be combined and spin evaporated in vacuo to give chloromethyl 6-(2-chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoate.

Workup

  1. customThe volatiles are removed by spin evaporation in vacuo
  2. dry with materialThe resulting cesium salt is dried by addition of toluene and removal of the volatiles under reduced pressure
  3. dissolutionThe dry cesium salt is dissolved in dimethylformamide (100 mL)
  4. filtrationThe mixture is filtered
  5. customto remove cesium bromide
  6. customthe volatiles are removed by spin evaporation in vacuo
  7. additionThe reaction mixture is diluted with dichloromethane (200 mL)
  8. extractionextracted with sodium bicarbonate solution
  9. washwashed with water
  10. dry with materialThe organic layer may be dried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto give crude product, which
  14. custommay be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent
  15. customspin evaporated in vacuo

Sources & evidence

ORD record
ord-32aa932dfe1447f6ad28fbbd04940535
Source dataset
uspto-grants-2010_07
Patent number
US07763612B2

Reaction notes

Loading…