Potassium Carbonate → 2-(1-(5-Bromo-2-nitrophenyl)-4-(tert-butoxycarbonyl)piperazin-2-yl)acetic acid

HRID 1896107

Reaction equation

HRID 1896107 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4](F)[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].[C:18]([O:22][C:23]([N:25]1[CH2:30][CH2:29][NH:28][CH:27]([CH2:31][C:32]([OH:34])=[O:33])[CH2:26]1)=[O:24])([CH3:21])([CH3:20])[CH3:19]>C(#N)C.O>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([N:28]2[CH2:29][CH2:30][N:25]([C:23]([O:22][C:18]([CH3:19])([CH3:20])[CH3:21])=[O:24])[CH2:26][CH:27]2[CH2:31][C:32]([OH:34])=[O:33])[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27833624-Bromo-2-fluoro-1-nitrobenzeneHCID 446077242-(4-(tert-Butoxycarbonyl)piperazin-2-yl)acetic acid

Product 1

HCID 672481792-(1-(5-Bromo-2-nitrophenyl)-4-(tert-butoxycarbonyl)piperazin-2-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

4-Bromo-2-fluoro-1-nitrobenzene (5.3 g, 24.1 mmol) was dissolved in acetonitrile (70 mL) and water (10 mL). To this mixture, potassium carbonate (10 g, 72.3 mmol) and 2-(4-(tert-butoxycarbonyl)piperazin-2-yl)acetic acid (7.1 g, 28.9 mmol) were added. The resulting mixture was heated at 70° C. for 2 days. The mixture thus obtained was concentrated and ethyl acetate was added. 1 N HCl was then added slowly to the reaction solution until pH=6. The water layer was separated and washed multiple times with ethyl acetate. The organic layers thus obtained were combined and concentrated. The crude material thus obtained was purified by silica gel chromatography eluting with a gradient of 0% to 10% of methanol in dichloromethane to afford the title compound. 1H NMR (300 MHz, DMSO-d6) δ ppm 12.28 (br s), 7.71-7.83 (m, 1 H), 7.56-7.66 (m, 1 H), 7.30-7.40 (m, 1 H), 3.56-3.82 (m, 3 H), 3.33-3.44 (m, 1 H), 2.99-3.24 (m, 2 H), 2.87 (m, 1 H), 2.32-2.47 (m, 1 H), 2.17-2.29 (m, 1 H), 1.32-1.51 (s, 9 H); MS (DCI+) m/z 444.1 (M+H)+.

Workup

  1. customThe mixture thus obtained
  2. concentrationwas concentrated
  3. additionethyl acetate was added
  4. addition1 N HCl was then added slowly to the reaction solution until pH=6
  5. customThe water layer was separated
  6. washwashed multiple times with ethyl acetate
  7. customThe organic layers thus obtained
  8. concentrationconcentrated
  9. customThe crude material thus obtained
  10. customwas purified by silica gel chromatography
  11. washeluting with a gradient of 0% to 10% of methanol in dichloromethane

Sources & evidence

ORD record
ord-2461c72fefd943ef838df856836c1877
Source dataset
uspto-grants-2013_08
Patent number
US08518933B2

Linked notes

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