Dimethylformamide → 4-tert-butyl-2-chloro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide

HRID 855255ノート

反応式

HRID 855255 の反応式
[C:1]([C:5]1[CH:10]=[CH:9][C:8](OS(C(F)(F)F)(=O)=O)=[C:7]([Cl:19])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].Cl.[F:21][C:22]([F:34])([F:33])[O:23][C:24]1[CH:25]=[C:26]([CH2:30][CH2:31][NH2:32])[CH:27]=[CH:28][CH:29]=1.C(N(CC)CC)C.C1C=CC(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN([CH:74]=[O:75])C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:74]([NH:32][CH2:31][CH2:30][C:26]2[CH:27]=[CH:28][CH:29]=[C:24]([O:23][C:22]([F:33])([F:34])[F:21])[CH:25]=2)=[O:75])=[C:7]([Cl:19])[CH:6]=1)([CH3:2])([CH3:3])[CH3:4]

参加物

7

反応物 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 17859607Trifluoro-methanesulfonic acid 4-tert-butyl-2-chloro-phenyl esterHCID 574385032-[3-(Trifluoromethoxy)phenyl]ethan-1-amine hydrochloride

生成物 1

HCID 695134924-tert-butyl-2-chloro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide収率 10%

試薬・触媒・溶媒 1

HCID 167845palladium(II) acetate触媒

反応条件

温度
70 °C

実験手順

633 mg (2 mmol) of trifluoro-methanesulfonic acid 4-tert-butyl-2-chloro-phenyl ester (prepared as described in example S80), 532 mg (2.2 mmol) of 2-(3-trifluoromethoxy-phenyl) ethyl amine hydrochloride and 223 mg (2.2 mmol) of triethyl amine were dissolved in 10 ml DMF. Under argon at rt 13.4 mg (0.06 mmol) of palladium acetate and 24.8 mg (0.06 mmol) of dppp were added. The reaction mixture was evacuated and charged with carbon monoxide gas three times. The reaction mixture was heated to 70° C. under a carbon monoxide atmosphere for 1 h. Water was added and the reaction mixture was extracted twice with EtOAc. The combined organic layers were washed with 1N aqueous HCl solution, once with saturated aqueous NaCl solution, dried over sodium sulfate, filtered and the solvent was evaporated. The residue was purified by column chromatography (60 g silica gel; heptane/EtOAc 7:3) to yield 82 mg (10%) of 4-tert-butyl-2-chloro-N-[2-(3-trifluoromethoxy-phenyl)-ethyl]-benzamide as a light yellow solid. 1H NMR (DMSO-d6, 300 MHz): δ 8.43 (t, 1H), 7.44-7.41 (m, 2H), 7.37 (d, 1H), 7.31 (d, 1H), 7.26-7.21 (m, 3H), 3.48 (q, 2H), 2.88 (t, 2H), 1.27 (s, 9H).

後処理

  1. customThe reaction mixture was evacuated
  2. additioncharged with carbon monoxide gas three times
  3. additionWater was added
  4. extractionthe reaction mixture was extracted twice with EtOAc
  5. washThe combined organic layers were washed with 1N aqueous HCl solution, once with saturated aqueous NaCl solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by column chromatography (60 g silica gel; heptane/EtOAc 7:3)

出典と根拠

ORDレコード
ord-6507f53cfde240c2bb4ba844f677dde9
出典データセット
uspto-grants-2007_08
特許番号
US07259183B2

反応ノート

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