Potassium Phosphate, Tribasic → (S)-[1-(4-cyclopropyl-2-fluoro-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester

HRID 1433795ノート

反応式

HRID 1433795 の反応式
[C:1]([O:5][C:6](=[O:28])[NH:7][C@H:8]([C:17](=[O:27])[NH:18][C:19]1[CH:24]=[CH:23][C:22](I)=[CH:21][C:20]=1[F:26])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].[CH:29]1(B(O)O)[CH2:31][CH2:30]1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C1(C)C=CC=CC=1.O.C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6](=[O:28])[NH:7][C@H:8]([C:17](=[O:27])[NH:18][C:19]1[CH:24]=[CH:23][C:22]([CH:29]2[CH2:31][CH2:30]2)=[CH:21][C:20]=1[F:26])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2]

参加物

9

反応物 4

HCID 62657Potassium Phosphate, TribasicHCID 75806Tricyclohexylphosphine2 回HCID 2760897Cyclopropylboronic acid2 回HCID 68619655(S)-[1-(2-fluoro-4-iodo-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester

生成物 1

HCID 68619453(S)-[1-(4-cyclopropyl-2-fluoro-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester収率 53.4%

試薬・触媒・溶媒 4

HCID 167845palladium(II) acetate触媒2 回HCID 962Water溶媒HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
100 °C

実験手順

To (S)-[1-(2-fluoro-4-iodo-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester (4.5 g, 9.0 mmol) and cyclopropylboronic acid (1.0 g, 11.7 mmol) in a mixture of toluene (40 mL) and water (2 mL) were added potassium phosphate tribasic (6.68 g, 31.5 mmol), tricyclohexylphosphine (0.50 g, 1.8 mmol) and palladium acetate (0.20 g, 0.89 mmol). The mixture was heated to 100° C. for 3 hours then additional tricyclohexylphosphine (0.25 g, 0.89 mmol) and palladium acetate (0.10 g, 0.45 mmol) were added. Heating at 100° C. was continued for an additional 3 hours before adding cyclopropylboronic acid (0.2 g, 2.33 mmol) and heating at 100° C. for a final period of 3 hours. The reaction mixture was diluted with ethyl acetate, washed with water (twice), brine (once), dried over sodium sulphate, filtered and concentrated in vacuo. The residue was purified by chromatography over silica gel eluted with 9:1 v/v dichloromethane in hexanes to afford (S)-[1-(4-cyclopropyl-2-fluoro-phenylcarbamoyl)-2-(4-fluoro-phenyl)-ethyl]-carbamic acid tert-butyl ester as a colorless solid (2.0 g, 53%).

後処理

  1. temperatureHeating at 100° C.
  2. temperatureheating at 100° C. for a final period of 3 hours
  3. washwashed with water (twice), brine (once),
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography over silica gel
  8. washeluted with 9:1 v/v dichloromethane in hexanes

出典と根拠

ORDレコード
ord-e03da0adb421440bbbd46ec13f72546f
出典データセット
uspto-grants-2009_11
特許番号
US07612212B2

反応ノート

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