(1,1'-Biphenyl)-3-carboxylic acid, 3'-amino-, methyl ester → Methyl 3'-(2-(tert-butoxycarbonylamino)ethylamino)biphenyl-3-carboxylate

HRID 1624199Notes

Reaction equation

HRID 1624199 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([C:14]([O:16][CH3:17])=[O:15])[CH:9]=2)[CH:5]=[CH:6][CH:7]=1.Br[CH2:19][CH2:20][NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25]>CN(C=O)C>[CH3:17][O:16][C:14]([C:10]1[CH:9]=[C:8]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([NH:1][CH2:19][CH2:20][NH:21][C:22]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:28])[CH:3]=2)[CH:13]=[CH:12][CH:11]=1)=[O:15]

Participants

4

Reactant 2

HCID 1394215(1,1'-Biphenyl)-3-carboxylic acid, 3'-amino-, methyl esterHCID 4103526tert-Butyl N-(2-bromoethyl)carbamate2×

Product 1

HCID 21191174Methyl 3'-(2-(tert-butoxycarbonylamino)ethylamino)biphenyl-3-carboxylateYield 16.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
55 °C

Procedure

A mixture of methyl 3′-aminobiphenyl-3-carboxylate (3.0 g, 13.22 mmol, 1.00 equiv.), tert-butyl 2-bromoethylcarbamate (3.0 g, 13.22 mmol, 1.00 equiv.) potassium carbonate (3.6 g, 26.09 mmol, 2.00 equiv.), and N,N′-dimethylformamide (20 mL) was heated at 50-60° C. for about 16 hours. Additional tert-butyl 2-bromoethylcarbamate (3.0 g, 13.22 mmol, 1.00 equiv) was added and the mixture was heated an additional 14 hours. The mixture was cooled to ambient temperature and partitioned between ethyl acetate and water. The organic layer was separated, washed with water, dried over sodium sulfate, filtered, and concentrated to afford a crude product that was purified by silica gel chromatography (petroleum ether/ethyl acetate (8:1) to give the title product as light-yellow oil (800 mg; yield=16%).

Workup

  1. temperaturethe mixture was heated an additional 14 hours
  2. temperatureThe mixture was cooled to ambient temperature
  3. custompartitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. washwashed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto afford a crude product that
  10. customwas purified by silica gel chromatography (petroleum ether/ethyl acetate (8:1)

Sources & evidence

ORD record
ord-5711b9d4df104e9090beb83c39affc95
Source dataset
uspto-grants-2014_07
Patent number
US08778998B2

Reaction notes

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