4-Methylmorpholine → (3-Benzylpiperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone

HRID 874923ノート

反応式

HRID 874923 の反応式
[F:1][C:2]([F:18])([F:17])[C:3]1[O:7][N:6]=[C:5]([C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([OH:13])=O)[N:4]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH2:43]([CH:50]1[CH2:55][CH2:54][CH2:53][NH:52][CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1.CN1CCOCC1>CN(C=O)C.CCOC(C)=O>[CH2:43]([CH:50]1[CH2:55][CH2:54][CH2:53][N:52]([C:11]([C:10]2[CH:14]=[CH:15][CH:16]=[C:8]([C:5]3[N:4]=[C:3]([C:2]([F:1])([F:18])[F:17])[O:7][N:6]=3)[CH:9]=2)=[O:13])[CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1

参加物

7

反応物 4

HCID 79724-MethylmorpholineHCID 1145513-BenzylpiperidineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 251808543-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid

生成物 1

HCID 53327767(3-Benzylpiperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone収率 44%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

3-(5-(Trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzoic acid (100 mg, 0.4 mmol) was dissolved in dry DMF (3 mL) and HATU (183 mg, 0.48 mmol) was added followed by 3-benzylpiperidine (75 mg, 0.42 mmol) and NMM (0.13 mL, 1.2 mmol) at 0° C. The reaction mixture was slowly warmed to room temperature and stirred for 8 h. The reaction mixture was then diluted with EtOAc and the organic layer was washed with water, 1.5N HCl solution and brine. The organic layer was dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether) to get (3-benzylpiperidin-1-yl)(3-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)phenyl)methanone (70 mg, yield 44%): 1H NMR (400 MHz, CDCl3) δ 8.15-8.01 (m, 2H), 7.59-7.47 (m, 2H), 7.32-7.21 (m, 2H), 7.06-6.97 (m, 3H), 4.63 (m, 1H), 3.59-3.56 (m, 1H), 2.83-2.51 (m, 4H), 1.93-1.84 (m, 3H), 1.26-1.22 (m, 2H). MS (ESI) m/z: Calculated for C22H20F3N3O2: 415.41. found: 416.2 (M+H)+.

後処理

  1. washthe organic layer was washed with water, 1.5N HCl solution and brine
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe crude product was purified by column chromatography (silica 60-120 mesh, eluant 10% EtOAc in petroleum ether)

出典と根拠

ORDレコード
ord-c570c13a2cef4026825f6b6c6b3cc4ef
出典データセット
uspto-grants-2015_03
特許番号
US08981084B2

反応ノート

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