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 552132Notes

Reaction equation

HRID 552132 reaction equation
[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]

Participants

4

Reactant 1

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
70 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-7b90b1988f5e4fa489807c0bb9fe650c
Source dataset
uspto-grants-2011_05
Patent number
US07951805B2

Reaction notes

Loading…