4-[(2-Bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl ester → 4-(3,3-Difluoro-2-oxo-2,3-dihydroindol-1-YL)-piperidine-1-carboxylic acid tert-butyl ester

HRID 552132ノート

反応式

HRID 552132 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([C:22](=[O:27])[C:23](Br)([F:25])[F:24])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2I)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]>CS(C)=O.[Cu]>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([N:14]2[C:15]3[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=3)[C:23]([F:25])([F:24])[C:22]2=[O:27])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

4

反応物 1

HCID 671716824-[(2-Bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]piperidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 866171214-(3,3-Difluoro-2-oxo-2,3-dihydroindol-1-YL)-piperidine-1-carboxylic acid tert-butyl ester収率 93%

試薬・触媒・溶媒 2

HCID 23978Copper触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
70 °C

実験手順

A mixture of 4-[(2-bromo-2,2-difluoroacetyl)-(2-iodophenyl)amino]-piperidine-1-carboxylic acid tert-butyl ester (1.670 g, 2.98 mmol) and copper (bronze, 0.480 g, 7.55 mmol) in DMSO (15 mL) was heated at 70° C. overnight. The reaction mixture was quenched with water at 0° C. and then extracted with ethyl acetate. The combined organic phase was washed with water and brine, dried over anhydrous Na2SO4 and concentrated. Purification of the residue by flash chromatography to afford the title compound in 93% yield (0.976 g). 1H NMR (300 MHz, CDCl3) δ 7.52-7.40 (m, 2H), 7.12 (t, J=7.5 Hz, 1H), 7.00 (t, J=8.1 Hz, 1H), 4.28-4.13 (m, 3H), 2.77 (t, J=12.9 Hz, 2H), 2.32-2.18 (m, 2H), 1.73 (d, J=12.9 Hz, 2H), 1.45 (s, 9H). 13C NMR (75 MHz, CDCl3) δ 165.5, 165.0, 164.6, 154.5, 142.6, 142.5, 142.4, 133.4, 125.0, 123.6, 120.6, 120.3, 120.0, 113.6, 110.9, 110.3, 107.0, 80.0, 77.5, 77.0, 76.6, 51.0, 43.2, 28.3, 27.9. MS (ES+) m/z 375.3 (M+Na).

後処理

  1. customThe reaction mixture was quenched with water at 0° C.
  2. extractionextracted with ethyl acetate
  3. washThe combined organic phase was washed with water and brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated
  6. customPurification of the residue by flash chromatography

出典と根拠

ORDレコード
ord-7b90b1988f5e4fa489807c0bb9fe650c
出典データセット
uspto-grants-2011_05
特許番号
US07951805B2

反応ノート

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