Bupropion → 2-[(6-(2-Chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone

HRID 2357755Notes

Reaction equation

HRID 2357755 reaction equation
[CH3:1][CH:2]([NH:12][C:13]([CH3:16])([CH3:15])[CH3:14])[C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([Cl:11])[CH:10]=1)=[O:4].Cl.ClC1C=C(C(=O)C(NC(C)(C)C)C)C=CC=1.C(N(CC)CC)C.[Cl:41][C:42]1[CH:47]=[C:46]([NH:48][CH2:49][C:50]2[O:51][CH:52]=[CH:53][CH:54]=2)[C:45]([C:55]([O:57][CH2:58][C:59]([Cl:62])([Cl:61])[Cl:60])=[O:56])=[CH:44][C:43]=1[S:63]([NH:66][CH2:67][O:68][C:69](=[O:79])[CH2:70][CH2:71][CH2:72][CH2:73][C:74]([O:76][CH2:77]Cl)=[O:75])(=[O:65])=[O:64]>C(#N)C>[Cl:41][C:42]1[CH:47]=[C:46]([NH:48][CH2:49][C:50]2[O:51][CH:52]=[CH:53][CH:54]=2)[C:45]([C:55]([O:57][CH2:58][C:59]([Cl:60])([Cl:62])[Cl:61])=[O:56])=[CH:44][C:43]=1[S:63]([NH:66][CH2:67][O:68][C:69](=[O:79])[CH2:70][CH2:71][CH2:72][CH2:73][C:74]([O:76][CH2:77][N:12]([C:13]([CH3:15])([CH3:14])[CH3:16])[CH:2]([CH3:1])[C:3]([C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([Cl:11])[CH:10]=1)=[O:4])=[O:75])(=[O:65])=[O:64]

Participants

6

Reactant 4

HCID 444BupropionHCID 8471TriethylamineHCID 62884Bupropion Hydrochloride2×HCID 68454251Chloromethyl 6-(2-chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoate

Product 1

HCID 596132162-[(6-(2-Chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

A solution of bupropion[1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride, (700) (U.S. Pat. No. 3,819,706; U.S. Pat. No. 3,885,046) (0.025 mole), triethylamine (0.055 mole) and acetonitrile (30 mL) are stirred with cooling on an ice bath. A solution of chloromethyl 6-(2-chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoate (0.025 mole) in acetonitrile (30 mL) is added dropwise. After the addition is complete, the reaction is heated to reflux for 2 hours. The reaction is cooled, the volatiles are removed by spin evaporation, and the residue is partitioned between dichloromethane and 5% aqueous sodium bicarbonate. The organic layer is 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 a solid that is recrystallized to give 2-[(6-(2-chloro-4-[(2-furanylmethyl)amino]-5-(2,2,2-trichloroethoxycarbonyl)phenylsulfonamidomethoxy)(6-oxo)hexanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone. See U.S. Pat. No. 5,104,870; Sandler et al., Organic Functional Group Preparations, (1968) p. 324.

Workup

  1. temperaturewith cooling on an ice bath
  2. additionAfter the addition
  3. temperaturethe reaction is heated
  4. temperatureto reflux for 2 hours
  5. temperatureThe reaction is cooled
  6. customthe volatiles are removed by spin evaporation
  7. customthe residue is partitioned between dichloromethane and 5% aqueous sodium bicarbonate
  8. washThe organic layer is washed with water
  9. dry with materialThe organic layer may be dried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give crude product, which
  13. custommay be purified by column chromatography on silica gel with hexanes/ethyl acetate as eluent
  14. customspin evaporated in vacuo
  15. customto give a solid
  16. customthat is recrystallized

Sources & evidence

ORD record
ord-af30aee849f1430abf6023109fed2695
Source dataset
uspto-grants-2010_07
Patent number
US07763612B2

Reaction notes

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