Potassium Carbonate → (R)-ethyl 1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate

HRID 42984ノート

反応式

HRID 42984 の反応式
O[CH2:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[CH2:8][C@@H:7]([NH:12][S:13]([CH:16]([CH3:18])[CH3:17])(=[O:15])=[O:14])[CH2:6]2.S(Cl)(Cl)=O.C(=O)([O-])[O-].[K+].[K+].[F:29][C:30]([F:42])([F:41])[C:31]1[C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[CH:34][NH:33][N:32]=1>C(Cl)Cl.CN(C=O)C>[CH3:17][CH:16]([S:13]([NH:12][C@H:7]1[CH2:6][C:5]2[C:9](=[CH:10][CH:11]=[C:3]([CH2:2][N:33]3[CH:34]=[C:35]([C:36]([O:38][CH2:39][CH3:40])=[O:37])[C:31]([C:30]([F:29])([F:41])[F:42])=[N:32]3)[CH:4]=2)[CH2:8]1)(=[O:15])=[O:14])[CH3:18]

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 24386Thionyl ChlorideHCID 67025426(R)-N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamideHCID 178469923HCID 178469923、化合物

生成物 1

HCID 67088231(R)-ethyl 1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate収率 86%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

実験手順

(R)—N-(5-(hydroxymethyl)-2,3-dihydro-1H-inden-2-yl)propane-2-sulfonamide (2.82 mmol, 760 mg) was dissolved in DCM (20 mL) and Thionyl Chloride (5.64 mmol, 0.409 mL, 671 mg) added and the solution stirred at room temperature. After 45 min the mixture was concentrated then azeotroped with DCM (4×10 mL) to give a yellow oil. To this oil was added DMF (10 mL) and potassium carbonate (8.46 mmol, 1170 mg) followed by ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (2.82 mmol, 587 mg). The mixture was heated to 60° C. with stirring for 1 h. The reaction was concentrated to remove DMF before partitioning between EtOAc/Water. The phases were mixed and separated and the aqueous phase further washed with EtOAc (×2). Combined organics were dried and concentrated to give a light yellow oil which was purified on silica eluting with 25% EtOAc/heptane. Desired fractions were collected and concentrated to give (R)-ethyl 1-((2-(1-methylethylsulfonamido)-2,3-dihydro-1H-inden-5-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate as a colourless solid (1.11 g, 86%).

後処理

  1. concentrationAfter 45 min the mixture was concentrated
  2. customthen azeotroped with DCM (4×10 mL)
  3. customto give a yellow oil
  4. temperatureThe mixture was heated to 60° C.
  5. stirringwith stirring for 1 h
  6. concentrationThe reaction was concentrated
  7. customto remove DMF
  8. custombefore partitioning between EtOAc/Water
  9. additionThe phases were mixed
  10. customseparated
  11. washthe aqueous phase further washed with EtOAc (×2)
  12. customCombined organics were dried
  13. concentrationconcentrated
  14. customto give a light yellow oil which
  15. customwas purified on silica eluting with 25% EtOAc/heptane
  16. customDesired fractions were collected
  17. concentrationconcentrated

出典と根拠

ORDレコード
ord-d0c8ca3c984148b98857b21126710b6e
出典データセット
uspto-grants-2013_09
特許番号
US08536214B2

反応ノート

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