Acetic Acid → N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide

HRID 2180170ノート

反応式

HRID 2180170 の反応式
[F:1][C:2]1[CH:3]=[C:4]([CH2:9][C:10]([NH:12][CH2:13][C:14]2([C:20]3[CH:25]=[CH:24][C:23]([I:26])=[CH:22][CH:21]=3)[CH2:19][CH2:18][NH:17][CH2:16][CH2:15]2)=[O:11])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH:27]1([CH:30]=O)[CH2:29][CH2:28]1.CC(O)=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C(Cl)CCl.CCOC(C)=O>[CH:27]1([CH2:30][N:17]2[CH2:18][CH2:19][C:14]([CH2:13][NH:12][C:10](=[O:11])[CH2:9][C:4]3[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=3)([C:20]3[CH:21]=[CH:22][C:23]([I:26])=[CH:24][CH:25]=3)[CH2:15][CH2:16]2)[CH2:29][CH2:28]1

参加物

7

反応物 4

HCID 176Acetic AcidHCID 123114CyclopropanecarboxaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 224903764-{[2-(3,5-Difluoro-phenyl)-acetylamino]-methyl}-4-(4-iodo-phenyl)-piperidine

生成物 1

HCID 68533825N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide収率 950%

試薬・触媒・溶媒 2

HCID 111,2-Dichloroethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a stirred solution of 4-{[2-(3,5-difluoro-phenyl)-acetylamino]-methyl}-4-(4-iodo-phenyl)-piperidine (0.038 g, ˜0.08 mmol) in ClCH2CH2Cl (0.5 mL) at room temperature under Ar was added cyclopropanecarboxaldehyde (0.008 mL, 0.096 mmol, 1.2 eq.) and HOAc (0.05 mL, 1% v/v). The mixture was stirred for 0.5 h then Na(OAc)3BH (0.026 g, 0.12 mmol, 1.5 eq.) was added and the mixture stirred for 16 h then diluted with EtOAc (5 mL) and washed with saturated aqueous NaHCO3 solution (5 mL) and saturated brine (5 mL). The organic layer was dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and dried under high vacuum to give N-[1-cyclopropylmethyl-4-(4-iodo-phenyl)-piperidin-4-ylmethyl]-2-(3,5-difluoro-phenyl)-acetamide (0.040 g, 0.76 mmol, 95%). MS (ESI): 525.2/526.2 (M+1).

後処理

  1. stirringthe mixture stirred for 16 h
  2. washwashed with saturated aqueous NaHCO3 solution (5 mL) and saturated brine (5 mL)
  3. dry with materialThe organic layer was dried over anhydrous Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated by rotary evaporation
  6. customdried under high vacuum

出典と根拠

ORDレコード
ord-52982ec9be404e3dbffcc9f920965596
出典データセット
uspto-grants-2005_05
特許番号
US06887889B2

反応ノート

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