Citric Acid → N-Butyloxycarbonyl-3-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-thiophene-2-sulfonamide

HRID 562555ノート

反応式

HRID 562555 の反応式
[N:1]1([CH2:7][C:8]2[CH:9]=[C:10]([C:14]3[CH:18]=[C:17]([CH2:19][CH:20]([CH3:22])[CH3:21])[S:16][C:15]=3[S:23]([NH:26]C(C)(C)C)(=[O:25])=[O:24])[CH:11]=[CH:12][CH:13]=2)[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].B(Cl)(Cl)Cl.N1(C2C=CC=CN=2)CCCC1.Cl[C:47]([O:49][CH2:50][CH2:51][CH2:52][CH3:53])=[O:48].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH2:50]([O:49][C:47]([NH:26][S:23]([C:15]1[S:16][C:17]([CH2:19][CH:20]([CH3:21])[CH3:22])=[CH:18][C:14]=1[C:10]1[CH:11]=[CH:12][CH:13]=[C:8]([CH2:7][N:1]2[CH2:5][CH2:4][CH2:3][C:2]2=[O:6])[CH:9]=1)(=[O:25])=[O:24])=[O:48])[CH2:51][CH2:52][CH3:53]

参加物

7

反応物 5

HCID 311Citric AcidHCID 25135Boron TrichlorideHCID 61140Butyl chloroformateHCID 110190202-(Pyrrolidin-1-yl)pyridineHCID 670049583-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide

生成物 1

HCID 11957018N-Butyloxycarbonyl-3-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-thiophene-2-sulfonamide収率 74%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a solution of 3-(3-pyrrolidine-2-one-1-ylmethylphenyl)-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (66.7 mg, 0.149 mmol; see step (a)) 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 (44.1 mg, 0.297 mmol) and butyl chloroformate (189.1 μL, 1.49 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 purified by LCMS (20-100% CH3CN in water) to give the title compound in 74% yield, over two steps, (54 mg, 0.110 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 purified by LCMS (20-100% CH3CN in water)

出典と根拠

ORDレコード
ord-3d77b314bd3841eab0a5596b725b0dfb
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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