Benzylamine → (+/-)-Tert-butyl 3-[3-(benzylamino)-4-chlorophenyl]-2-cyclobutylpropanoate

HRID 1476103ノート

反応式

HRID 1476103 の反応式
CC(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH2:53]([NH2:60])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1.Br[C:62]1[CH:63]=[C:64]([CH2:69][CH:70]([CH:78]2[CH2:81][CH2:80][CH2:79]2)[C:71]([O:73][C:74]([CH3:77])([CH3:76])[CH3:75])=[O:72])[CH:65]=[CH:66][C:67]=1[Cl:68]>C1(C)C=CC=CC=1>[CH2:53]([NH:60][C:66]1[CH:65]=[C:64]([CH2:69][CH:70]([CH:78]2[CH2:79][CH2:80][CH2:81]2)[C:71]([O:73][C:74]([CH3:77])([CH3:76])[CH3:75])=[O:72])[CH:63]=[CH:62][C:67]=1[Cl:68])[C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=1

参加物

6

反応物 4

HCID 7504BenzylamineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 58288258(+/-)-Tert-butyl 3-(3-bromo-4-chlorophenyl)-2-cyclobutylpropanoate

生成物 1

HCID 58288306(+/-)-Tert-butyl 3-[3-(benzylamino)-4-chlorophenyl]-2-cyclobutylpropanoate

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
110 °C

実験手順

Under argon, 848.6 mg (8.83 mmol) of sodium tert-butoxide, 337 mg (0.39 mmol) of tris(dibenzylidenacetone)dipalladium and 183 mg (0.29 mmol) of rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl were weighed out into a dry flask, kept under high vacuum for 10 min and then vented with argon. 5 ml of abs. toluene, 0.96 ml (8.83 mmol) of benzylamine and a solution of 2.75 g (7.36 mmol) of (+/−)-tert-butyl 3-(3-bromo-4-chlorophenyl)-2-cyclobutylpropanoate in 5 ml of abs. toluene were added in succession. Three more times, the reaction mixture was evacuated and in each case vented with argon, and the mixture was then stirred at 110° C. for 3 h. After cooling, the reaction mixture was added to saturated aqueous ammonium chloride solution. The mixture was extracted three times with ethyl acetate. The organic phases were combined, dried over magnesium sulphate and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (mobile phase cyclohexane/dichloromethane 4:1 to 2:1, then pure dichloromethane) This gave 1.95 g of the title compound (65.1% of theory).

後処理

  1. customThree more times, the reaction mixture was evacuated and in each case
  2. temperatureAfter cooling
  3. additionthe reaction mixture was added to saturated aqueous ammonium chloride solution
  4. extractionThe mixture was extracted three times with ethyl acetate
  5. dry with materialdried over magnesium sulphate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by chromatography on silica gel (mobile phase cyclohexane/dichloromethane 4:1 to 2:1

出典と根拠

ORDレコード
ord-52b6d7a13029491f99aeddca84832faf
出典データセット
uspto-grants-2015_04
特許番号
US09018414B2

反応ノート

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