Borane → ((3s,4r)-1-Benzyl-4-o-tolyl-pyrrolidin-3-yl)-methyl-amine

HRID 1365919ノート

反応式

HRID 1365919 の反応式
[CH2:1]([N:8]1[CH2:12][CH:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])[CH:10]([NH2:20])[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:21]([O-])([O-])=O.[K+].[K+].ClC(OCC)=O.B>C1COCC1.O>[CH2:1]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[CH3:19])[C@H:10]([NH:20][CH3:21])[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

参加物

7

反応物 4

HCID 6331BoraneHCID 10928Ethyl chloroformateHCID 11430Potassium CarbonateHCID 66940494rac-(3S,4R)-1-benzyl-4-o-tolyl-pyrrolidin-3-ylamine

生成物 1

HCID 66940639((3s,4r)-1-Benzyl-4-o-tolyl-pyrrolidin-3-yl)-methyl-amine収率 35.1%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
65 °C

実験手順

To a solution of rac-(3S,4R)-1-benzyl-4-o-tolyl-pyrrolidin-3-ylamine (0.73 g, 2.74 mmol) in THF (15 ml) was added a solution of K2CO3 (0.75 mg, 5.48 mmol) in H2O (5 ml). After 10 minutes, ethyl chloroformate (0.27 ml, 2.87 mmol) was added and stirring was continued at RT for an additional 2 h. The intermediate carbamate was then extracted with Et2O, dried over Na2SO4 and concentrated under vacuo to give viscous oil. The oil was taken up in THF (10 ml) and a solution of borane in THF (1M) was added (11 ml). The reaction mixture was then heated at 65° C. over night, cooled to RT and carefully quenched with conc. HCl (5 ml). The mixture was then heated at 80° C. for 2 h, cooled to RT, concentrated under vacuo, diluted with Et2O (60 ml) and neutralized with an aqueous solution of NaHCO3. The organic phases were dried over Na2SO4 and the product purified by flash chromatography (SiO2, CH2Cl2/MeOH 9:1) to afford 0.27 g (35%) of rac-((3S,4R)-1-benzyl-4-o-tolyl-pyrrolidin-3-yl)-methyl-amine as a colorless oil. ES-MS m/e: 281.3 (M+H+).

後処理

  1. waitwas continued at RT for an additional 2 h
  2. extractionThe intermediate carbamate was then extracted with Et2O
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under vacuo
  5. customto give viscous oil
  6. temperaturecooled to RT
  7. customcarefully quenched with conc. HCl (5 ml)
  8. temperatureThe mixture was then heated at 80° C. for 2 h
  9. temperaturecooled to RT
  10. concentrationconcentrated under vacuo
  11. additiondiluted with Et2O (60 ml)
  12. dry with materialThe organic phases were dried over Na2SO4
  13. customthe product purified by flash chromatography (SiO2, CH2Cl2/MeOH 9:1)

出典と根拠

ORDレコード
ord-a4a9553a398a410ba18a3ebd327a5d63
出典データセット
uspto-grants-2011_02
特許番号
US07893062B2

反応ノート

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