Triethylamine → {2-[7-(2,4-Bis-trifluoromethyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester

HRID 1072591ノート

反応式

HRID 1072591 の反応式
[C:1]([O:5][C:6]([NH:8][C:9]([CH3:29])([CH3:28])[CH2:10][C:11]1[C:19]2[C:14](=[C:15](OS(C(F)(F)F)(=O)=O)[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[F:37][C:38]([F:53])([F:52])[C:39]1[CH:44]=[C:43]([C:45]([F:48])([F:47])[F:46])[CH:42]=[CH:41][C:40]=1B(O)O>CN(C)C=O.[Cl-].[Na+].O.C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]([CH3:29])([CH3:28])[CH2:10][C:11]1[C:19]2[C:14](=[C:15]([C:40]3[CH:41]=[CH:42][C:43]([C:45]([F:48])([F:46])[F:47])=[CH:44][C:39]=3[C:38]([F:37])([F:52])[F:53])[CH:16]=[CH:17][CH:18]=2)[NH:13][CH:12]=1)([CH3:3])([CH3:2])[CH3:4]

参加物

8

反応物 3

HCID 8471TriethylamineHCID 27826672,4-Bis(trifluoromethyl)phenylboronic acidHCID 86595245trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester

生成物 1

HCID 86595246{2-[7-(2,4-Bis-trifluoromethyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester収率 89.2%

試薬・触媒・溶媒 4

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
100 °C

実験手順

To a solution of trifluoro-methanesulfonic acid 3-(2-tert-butoxycarbonylamino-2-methyl-propyl)-1H-indol-7-yl ester (262 mg, 0.600 mmol) in dimethylformamide (3.5 mL) is added triethylamine (0.11 mL, 0.780 mmol), tetrakis(triphenylphosphine)-palladium (28 mg, 0.0240 mmol) and 2,4-bistrifluoromethylbenzeneboronic acid (201 mg, 0.780 mmol). The mixture is heated to 100° C. for 20 hours, then cooled, diluted with brine and ethyl acetate. The organics are washed seven times with brine then dried over anhydrous sodium sulfate, filtered and evaporated in vacuo. The residue is purified using silica gel chromatography (hexane/20% ethyl acetate, hexane gradient elution) to give 268 mg of {2-[7-(2,4-Bis-trifluoromethyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester (89%). FDMS m/e=501 (M++1). The title amine is prepared from {2-[7-(2,4-Bis-trifluoromethyl-phenyl)-1H-indol-3-yl]-1,1-dimethyl-ethyl}-carbamic acid tert-butyl ester as described above for Amine 1 (208 mg, 100%). FDMS m/e=401 (M++1).

後処理

  1. temperaturecooled
  2. washThe organics are washed seven times with brine
  3. dry with materialthen dried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated in vacuo
  6. customThe residue is purified
  7. washsilica gel chromatography (hexane/20% ethyl acetate, hexane gradient elution)

出典と根拠

ORDレコード
ord-1c22d9b8bf264e2ba07e3b835aba01e3
出典データセット
uspto-grants-2005_06
特許番号
US06911463B2

反応ノート

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