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 552132노트

반응식

HRID 552132 반응식
[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]

참가 물질

4

반응물 1

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

생성물 1

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

시약·촉매·용매 2

HCID 23978Copper촉매HCID 679Dimethyl Sulfoxide용매

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온도
70 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-7b90b1988f5e4fa489807c0bb9fe650c
출처 데이터셋
uspto-grants-2011_05
특허 번호
US07951805B2

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