Citric Acid → N-Butyloxycarbonyl-3-(3-pyrrolidine-2,5-dione-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide

HRID 562553ノート

反応式

HRID 562553 の反応式
[N:1]1([CH2:8][C:9]2[CH:10]=[C:11]([C:15]3[CH:19]=[C:18]([CH2:20][CH:21]([CH3:23])[CH3:22])[S:17][C:16]=3[S:24]([NH:27]C(C)(C)C)(=[O:26])=[O:25])[CH:12]=[CH:13][CH:14]=2)[C:5](=[O:6])[CH2:4][CH2:3][C:2]1=[O:7].B(Cl)(Cl)Cl.N1(C2C=CC=CN=2)CCCC1.Cl[C:48]([O:50][CH2:51][CH2:52][CH2:53][CH3:54])=[O:49].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH2:51]([O:50][C:48]([NH:27][S:24]([C:16]1[S:17][C:18]([CH2:20][CH:21]([CH3:23])[CH3:22])=[CH:19][C:15]=1[C:11]1[CH:12]=[CH:13][CH:14]=[C:9]([CH2:8][N:1]2[C:5](=[O:6])[CH2:4][CH2:3][C:2]2=[O:7])[CH:10]=1)(=[O:25])=[O:26])=[O:49])[CH2:52][CH2:53][CH3:54]

参加物

7

反応物 5

HCID 311Citric AcidHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 670045673-(3-pyrrolidine-2,5-dione-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

生成物 1

HCID 11849856N-Butyloxycarbonyl-3-(3-pyrrolidine-2,5-dione-1-ylmethylphenyl)-5-iso-butylthiophene-2-sulfonamide収率 76%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 3-(3-pyrrolidine-2,5-dione-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (95.0 mg, 0.205 mmol; see step (f)) in CH2Cl2 (2 mL) was added BCl3 (0.6 mL, 1.0 M in hexane) and the reaction mixture was stirred for 1 h at ambient temperature. The reaction mixture was concentrated in vacuo. Water (5 mL) was added to the residue and this was then extracted with EtOAc. The combined organic phase was washed with water and brine, dried (over anhydrous MgSO4) and concentrated in vacuo. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (91.3 mg, 0.616 mmol) and butyl chloroformate (261.1 μL, 2.05 mmol) and the reaction mixture was stirred overnight. Citric acid (3 mL, 10% aq) was added to the reaction mixture, which was then extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue was purified by LCMS (Liquid Chromatography Mass Spectrum; 25-100% CH3CN in water) to give the title compound in 76% yield, over two steps, (79.1 mg, 0.156 mmol).

後処理

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. additionWater (5 mL) was added to the residue
  3. extractionthis was then extracted with EtOAc
  4. washThe combined organic phase was washed with water and brine
  5. dry with materialdried (over anhydrous MgSO4)
  6. concentrationconcentrated in vacuo
  7. dissolutionTo the crude product dissolved in pyridine (1.5 mL)
  8. stirringthe reaction mixture was stirred overnight
  9. extractionwas then extracted with EtOAc
  10. dry with materialdried (over anhydrous MgSO4)
  11. concentrationconcentrated in vacuo
  12. customthe residue was purified by LCMS (Liquid Chromatography Mass Spectrum; 25-100% CH3CN in water)

出典と根拠

ORDレコード
ord-e99a81f95514481586097500feec4fa7
出典データセット
uspto-grants-2011_11
特許番号
US08067418B2

反応ノート

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