Toluene → 1-{2-[5-(4-Chloro-phenyl)-oxazol-2-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine

HRID 1051400ノート

反応式

HRID 1051400 の反応式
ClC1C=CC(C(=O)[CH2:9][NH:10][C:11](=[O:35])[CH2:12][CH:13]([CH2:18][N:19]2[CH2:24][CH2:23][CH2:22][CH:21]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=3)[CH2:20]2)[C:14]([F:17])([F:16])[F:15])=CC=1.O=P(Cl)(Cl)[Cl:39].[C:42]1([CH3:48])[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=1.C([O-])([O-])=O.[Na+].[Na+]>C(OCC)(=O)C>[Cl:39][C:45]1[CH:46]=[CH:47][C:42]([C:48]2[O:35][C:11]([CH2:12][CH:13]([C:14]([F:17])([F:15])[F:16])[CH2:18][N:19]3[CH2:24][CH2:23][CH2:22][CH:21]([C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:32])([F:33])[F:34])[CH:26]=4)[CH2:20]3)=[N:10][CH:9]=2)=[CH:43][CH:44]=1

参加物

6

反応物 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 24813Phosphorus oxychlorideHCID 90133968N-(2-(4-chlorophenyl)-2-oxoethyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamide

生成物 1

HCID 752013741-{2-[5-(4-Chloro-phenyl)-oxazol-2-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

In a 5 mL round-bottomed flask, N-(2-(4-chlorophenyl)-2-oxoethyl)-4,4,4-trifluoro-3-((3-(3-(trifluoromethyl)phenyl)piperidin-1-yl)methyl)butanamide (30 mg, 56.1 μmol) and POCl3 (51.6 mg, 336 μmol) were combined with toluene (1 ml) to give a colorless solution. The reaction mixture was heated to 100° C. and stirred for 4 h. The reaction mixture was diluted with ethyl acetate (30 ml), poured into ice-water and made basic with saturated solution of Na2CO3. The organic layer was separated and washed with brine and H2O, dried over MgSO4, filtered and concentrated in vacuo to give an oil. The resultant oil was purified by flash chromatography (silica gel, 12 g, 0% to 50% ethyl acetate in hexane gradient) to afford 1-{2-[5-(4-chloro-phenyl)-oxazol-2-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine as an oil. It was dissolved in Et2O/Hexane, treated with 4N HCl in dioxane (0.1 ml) and concentrated in vacuo to afford 23 mg (76%) of 1-{2-[5-(4-chloro-phenyl)-oxazol-2-ylmethyl]-3,3,3-trifluoro-propyl}-3-(3-trifluoromethyl-phenyl)-piperidine hydrochloride as a white solid. MH+=517.

後処理

  1. customto give a colorless solution
  2. customThe organic layer was separated
  3. washwashed with brine and H2O
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give an oil
  8. customThe resultant oil was purified by flash chromatography (silica gel, 12 g, 0% to 50% ethyl acetate in hexane gradient)

出典と根拠

ORDレコード
ord-2ca2c454b95a4d71993a5bf63918575b
出典データセット
uspto-grants-2016_07
特許番号
US09388172B2

反応ノート

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