Bupropion → 2-[(4-(3-(5-(Aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone

HRID 2357743ノート

反応式

HRID 2357743 の反応式
[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.[NH2:41][S:42]([C:45]1[C:46]([Cl:74])=[CH:47][C:48]([NH:67][CH2:68][C:69]2[O:70][CH:71]=[CH:72][CH:73]=2)=[C:49]([CH:66]=1)[C:50]([O:52][CH2:53][CH2:54][CH2:55][O:56][C:57](=[O:65])[CH2:58][CH2:59][C:60]([O:62][CH2:63]Cl)=[O:61])=[O:51])(=[O:44])=[O:43]>C(#N)C>[NH2:41][S:42]([C:45]1[C:46]([Cl:74])=[CH:47][C:48]([NH:67][CH2:68][C:69]2[O:70][CH:71]=[CH:72][CH:73]=2)=[C:49]([CH:66]=1)[C:50]([O:52][CH2:53][CH2:54][CH2:55][O:56][C:57](=[O:65])[CH2:58][CH2:59][C:60]([O:62][CH2:63][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:61])=[O:51])(=[O:43])=[O:44]

参加物

6

反応物 4

HCID 444BupropionHCID 8471TriethylamineHCID 62884Bupropion HydrochlorideHCID 68457545Chloromethyl 4-(3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoate

生成物 1

HCID 684542782-[(4-(3-(5-(Aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒2 回

実験手順

A solution of bupropion[1-(3-chlorophenyl)-2-[(1,1-dimethylethyl)amino]-1-propanone hydrochloride (700), (U.S. Pat. No. 3,819,706 and U.S. Pat. No. 3,885,046) (0.025 mole), triethylamine (0.055 mole) and acetonitrile (30 mL) is stirred with cooling on an ice bath. A solution of chloromethyl 4-(3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoate (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 removed by spin evaporation, and the residue 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 is 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 may be recrystallized to give 2-[(4-(3-(5-(aminosulfonyl)-4-chloro-2-[(2-furanylmethyl)amino]benzoyloxy)propoxy)(4-oxo)butanoyloxymethyl)(1,1-dimethylethyl)amino]-1-(3-chlorophenyl)-1-propanone (920). See eg., U.S. Pat. No. 5,104,870 and Sandler, et al., Organic Functional Group Preparations, p. 324 (1968).

後処理

  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 removed by spin evaporation
  7. customthe residue partitioned between dichloromethane and 5% aqueous sodium bicarbonate
  8. washThe organic layer is washed with water
  9. dry with materialThe organic layer is 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 may be recrystallized

出典と根拠

ORDレコード
ord-dd5300488f5c4c5ab75196dd9aa1c016
出典データセット
uspto-grants-2010_07
特許番号
US07763612B2

反応ノート

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