Ethanol → (+/-)-cis-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-[4-(phenylmethyl)-1-piperazinyl]piperidine

HRID 1060189ノート

反応式

HRID 1060189 の反応式
[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[C:6]([N:8]1[CH2:13][CH2:12][C:11](=O)[CH2:10][CH:9]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7].[C:31]1([CH2:37][N:38]2[CH2:43][CH2:42][NH:41][CH2:40][CH2:39]2)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.C([BH3-])#N.[Na+].C(O)C>C(Cl)Cl.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].O>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([CH:22]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:24]=1)[C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([N:41]2[CH2:42][CH2:43][N:38]([CH2:37][C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:39][CH2:40]2)[CH2:10][C@@H:9]1[CH2:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:7]

参加物

8

反応物 4

HCID 702EthanolHCID 759941-BenzylpiperazineHCID 5003444Sodium cyanoborohydrideHCID 11026356(+/-)-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinone

生成物 1

HCID 86619157(+/-)-cis-1-[3,5-Bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-[4-(phenylmethyl)-1-piperazinyl]piperidine収率 26.9%

試薬・触媒・溶媒 3

HCID 11026Titanium isopropoxide触媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒2 回

実験手順

Titanium(IV)isopropoxide (16.5 g) was added to a mixture of intermediate 3 (21.5 g) and 1-(phenylmethyl)piperazine (8.81 g) in DCM (35 ml). The mixture was stirred for 3 hours at RT. Sodium cyanoborohydride (2.85 g) and ethanol (70 ml) were added and the resulting reaction mixture was stirred overnight at RT. Water (5 ml) and DCM were added. The biphasic mixture was filtered over dicalite, and the filter residue was washed with DCM. The organic layer was separated, dried, filtered and the solvent was evaporated. The residue was crystallized from CH3CN and the precipitate was filtered off and dried, yielding 7.93 g (26.9%) of (±)-cis-1-[3,5-bis(trifluoromethyl)benzoyl]-2-(phenylmethyl)-4-[4-(phenylmethyl)-1-piperazinyl]piperidine (compound 16; mp. 143.8° C.).

後処理

  1. customthe resulting reaction mixture
  2. stirringwas stirred overnight at RT
  3. filtrationThe biphasic mixture was filtered over dicalite
  4. washthe filter residue was washed with DCM
  5. customThe organic layer was separated
  6. customdried
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was crystallized from CH3CN
  10. filtrationthe precipitate was filtered off
  11. customdried

出典と根拠

ORDレコード
ord-7b761f7b615643d689884417a6ed5220
出典データセット
uspto-grants-2003_02
特許番号
US06521621B1

反応ノート

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