Hydrochloric Acid → N-(3,4-Difluorophenyl)-alpha-(4-fluorophenyl)-1-[2-(1-naphthalenyloxy)ethyl]-4-piperidinemethanamine dihydrochloride

HRID 1614654ノート

反応式

HRID 1614654 の反応式
[F:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]([C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)[CH:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[CH:5]=[CH:6][C:7]=1[F:8].Br[CH2:25][CH2:26][O:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:31]=[CH:30][CH:29]=1.C(=O)(O)[O-].[Na+].[I-].[Na+].[ClH:45]>C(O)CCC.C(Cl)Cl>[ClH:45].[ClH:45].[F:1][C:2]1[CH:3]=[C:4]([NH:9][CH:10]([C:17]2[CH:18]=[CH:19][C:20]([F:23])=[CH:21][CH:22]=2)[CH:11]2[CH2:16][CH2:15][N:14]([CH2:25][CH2:26][O:27][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[CH:31]=[CH:30][CH:29]=3)[CH2:13][CH2:12]2)[CH:5]=[CH:6][C:7]=1[F:8]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 110759061-(2-Bromoethoxy)naphthaleneHCID 197720314-[[(3,4-Difluorophenyl)amino](4-fluorophenyl)methyl]piperidine

生成物 1

HCID 19771980N-(3,4-Difluorophenyl)-alpha-(4-fluorophenyl)-1-[2-(1-naphthalenyloxy)ethyl]-4-piperidinemethanamine dihydrochloride収率 53.1%

試薬・触媒・溶媒 2

HCID 2631-Butanol溶媒HCID 6344Dichloromethane溶媒

実験手順

A mixture of 4-[[(3,4-difluorophenyl)amino](4-fluorophenyl)methyl]piperidine (5.41 g, 0.0169 mol), 1-(2-bromoethoxy)naphthalene (4.23 g, 0.0169 mol) and sodium bicarbonate (5.53 g, 0.059 mol) in 350 mL of 1-butanol containing sodium iodide (0.2 g) was heated 20 h at reflux. The reaction was concentrated to dryness and partitioned between chloroform and water. The chloroform layer was washed with 5% sodium hydroxide and dried (Na2SO4). Chloroform was removed to give a brown oil. The oil was dissolved in methylene chloride and placed on a silica gel column for flash chromatography. Elution was accomplished using 1% methanol-methylene chloride and 2% methanol-methylene chloride. Fractions of similar purity were combined and solvents removed to give a fluffy grey material. This material was converted to the HCl salt and the salt was recrystallized from methanol-diethyl ether to give a whitish-grey solid. The material was dried 16 h in vacuo at 80° C. This process provided 5.06 g (53.1%) of greyish material, mp 212°-215° C. (dec).

後処理

  1. temperaturewas heated 20 h
  2. temperatureat reflux
  3. concentrationThe reaction was concentrated to dryness
  4. custompartitioned between chloroform and water
  5. washThe chloroform layer was washed with 5% sodium hydroxide
  6. dry with materialdried (Na2SO4)
  7. customChloroform was removed
  8. customto give a brown oil
  9. washElution
  10. customsolvents removed
  11. customto give a fluffy grey material
  12. customthe salt was recrystallized from methanol-diethyl ether
  13. customto give a whitish-grey solid
  14. customThe material was dried 16 h in vacuo at 80° C

出典と根拠

ORDレコード
ord-a516fed9f52f42298622dabd27e3e88b
出典データセット
uspto-grants-1993_03
特許番号
US05198449

反応ノート

読み込み中…