Oxalic Acid → 4-[Bis(4-fluorophenyl)hydroxymethyl]-1-piperidinebutanamide ethanedioate

HRID 345492ノート

反応式

HRID 345492 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)([CH:10]2[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[OH:9])=[CH:4][CH:3]=1.Cl[CH2:24][CH2:25][CH2:26][C:27]([NH2:29])=[O:28].C(=O)([O-])[O-].[Na+].[Na+].[I-].[K+].[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40]>CN(C)C=O.O>[C:38]([OH:43])(=[O:42])[C:39]([OH:41])=[O:40].[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)([OH:9])[CH:10]2[CH2:11][CH2:12][N:13]([CH2:24][CH2:25][CH2:26][C:27]([NH2:29])=[O:28])[CH2:14][CH2:15]2)=[CH:4][CH:3]=1

参加物

8

反応物 5

HCID 971Oxalic AcidHCID 4875Potassium IodideHCID 10340Sodium CarbonateHCID 755644-ChlorobutyramideHCID 11208889Bis(4-fluorophenyl)(piperidin-4-yl)methanol

生成物 1

HCID 867451674-[Bis(4-fluorophenyl)hydroxymethyl]-1-piperidinebutanamide ethanedioate収率 9%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 6.1 g (0.020 mole) of α,α-bis(4-fluorophenyl)-4-piperidinemethanol, 4.9 g (0.040 mole) of 4-chlorobutanamide, 8.5 g (0.080 mole) of anhydrous sodium carbonate and 0.4 g (0.002 mole) of potassium iodide in 100 mL of N,N-dimethylformamide was stirred at ambient temperature for 24 h. The mixture was poured into 1.5 L of water and extracted twice with 500 mL portions of ethyl acetate. The ethyl acetate fractions were combined, washed with water and brine, dried (MgSO4), and concentrated under reduced pressure to give a dark oil. The oil was purified by column chromatography using 250 g of silica gel on a 65 cm×4 cm column eluted with methanol-methylene chloride (1:2). The fractions containing the desired product were combined and concentrated under reduced pressure. The residue was partitioned between methylene chloride and water. The methylene chloride layer was washed with water and brine, dried (MgSO4) and concentrated under reduced pressure to give a glass. The glass was converted to the oxalic acid salt, and the solid was recrystallized from ethyl acetate/2-propanol to yield 0.7 g (9%) of the title compound as a white solid containing 0.25 mole H2O, mp 177°-179° C.

後処理

  1. extractionextracted twice with 500 mL portions of ethyl acetate
  2. washwashed with water and brine
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated under reduced pressure
  5. customto give a dark oil
  6. customThe oil was purified by column chromatography
  7. washeluted with methanol-methylene chloride (1:2)
  8. additionThe fractions containing the desired product
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was partitioned between methylene chloride and water
  11. washThe methylene chloride layer was washed with water and brine
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated under reduced pressure
  14. customto give a glass
  15. customthe solid was recrystallized from ethyl acetate/2-propanol

出典と根拠

ORDレコード
ord-aec586dfebeb4ff5ac6ea0f33730b9ad
出典データセット
uspto-grants-1991_10
特許番号
US05057524

反応ノート

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