Thionyl Chloride → Methyl alpha-phenyl-1-[4-[[[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl]carbonyl]amino]phenyl]-4-piperidineacetate

HRID 1375959ノート

反応式

HRID 1375959 の反応式
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:10]([C:15](O)=[O:16])=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:4]=1.S(Cl)(Cl)=O.[NH2:24][C:25]1[CH:30]=[CH:29][C:28]([N:31]2[CH2:36][CH2:35][CH:34]([CH:37]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:38]([O:40][CH3:41])=[O:39])[CH2:33][CH2:32]2)=[CH:27][CH:26]=1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[C:42]1([CH:37]([CH:34]2[CH2:35][CH2:36][N:31]([C:28]3[CH:27]=[CH:26][C:25]([NH:24][C:15]([C:10]4[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=4[C:6]4[CH:7]=[CH:8][C:3]([C:2]([F:1])([F:18])[F:19])=[CH:4][CH:5]=4)=[O:16])=[CH:30][CH:29]=3)[CH2:32][CH2:33]2)[C:38]([O:40][CH3:41])=[O:39])[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=1

参加物

7

反応物 4

HCID 24386Thionyl ChlorideHCID 552514'-(Trifluoromethyl)(1,1'-biphenyl)-2-carboxylic acidHCID 81531DiisopropylethylamineHCID 22499374(+/-)-Methyl 1-(4-aminophenyl)-alpha-phenyl-4-piperidineacetate

生成物 1

HCID 22499403Methyl alpha-phenyl-1-[4-[[[4'-(trifluoromethyl)-[1,1'-biphenyl]-2-yl]carbonyl]amino]phenyl]-4-piperidineacetate収率 77.3%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

DMF (0.5 ml) was added to a solution of 4′-(trifluoromethyl)-[1,1′-biphenyl]-2-carboxylic acid (0.014 mole) in DCM (50 ml) and thionyl chloride (0.028 mole). The mixture was stirred and refluxed for one hour. The solvent was evaporated. DCM (50 ml) was added twice and the solvent was evaporated. The residue was dissolved in DCM (20 ml) and this solution was added to a mixture of intermediate (15) (0.014 mole) and DIPEA (0.028 mole) in DCM (80 ml). The mixture was stirred at room temperature for three hours and washed with water. The organic layer was dried and the solvent was evaporated. The residue was crystallized from 2-propanol. The precipitate was filtered off and dried, yielding 6.2 g of methyl α-phenyl-1-[4-[[[4′-(trifluoromethyl)-[1,1′-biphenyl]-2-yl]carbonyl]amino]phenyl]-4-piperidineacetate (melting point 151° C.) identified as compound No. 39 in the following table F-1.

後処理

  1. temperaturerefluxed for one hour
  2. customThe solvent was evaporated
  3. additionDCM (50 ml) was added twice
  4. customthe solvent was evaporated
  5. dissolutionThe residue was dissolved in DCM (20 ml)
  6. stirringThe mixture was stirred at room temperature for three hours
  7. washwashed with water
  8. customThe organic layer was dried
  9. customthe solvent was evaporated
  10. customThe residue was crystallized from 2-propanol
  11. filtrationThe precipitate was filtered off
  12. customdried

出典と根拠

ORDレコード
ord-b8ddecb39ef7497a92017e216d8c89f1
出典データセット
uspto-grants-2007_01
特許番号
US07169796B2

反応ノート

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