Sodium Carbonate → Methyl 3-amino-2'-fluorobiphenyl-4-carboxylate

HRID 661959Notes

Reaction equation

HRID 661959 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](Br)=[CH:6][C:5]=1[NH2:11].[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=1B(O)O.C(=O)([O-])[O-].[Na+].[Na+]>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:1][O:2][C:3]([C:4]1[CH:9]=[CH:8][C:7]([C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=2[F:13])=[CH:6][C:5]=1[NH2:11])=[O:12]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 17871390Methyl 2-Amino-4-bromobenzoate

Product 1

HCID 66605809Methyl 3-amino-2'-fluorobiphenyl-4-carboxylateYield 81%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

Step 1 A mixture of methyl-2-amino-4-bromobenzoate (3.06 g, 13.3 mmol), 2-fluorophenylboronic acid (2.23 g, 16.0 mmol), tetrakis(triphenylphosphine)palladium (1.54 g, 1.33 mmol) and 1 M aqueous sodium carbonate (16.6 mL, 16.6 mmol) in 1,2-dimethoxyethane (66.5 mL) was stirred at 90° C. overnight. The mixture was cooled to rt, filtered through a pad of Celite and the solids were rinsed with EtOAc. The filtrate was washed with water and brine, dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from hexane to 90:10 hexane-EtOAc) to provide methyl-3-amino-2′-fluorobiphenyl-4-carboxylate (2.63 g, 81%) as a white solid. 1H NMR (400 MHz, chloroform-d) δ 7.90 (d, J=8.25 Hz, 1H), 7.38-7.46 (m, 1H), 7.27-7.35 (m, 1H), 7.08-7.22 (m, 2H), 6.85 (s, 1H), 6.82 (d, J=8.25 Hz, 1H), 5.83 (br s, 1H), 3.88 (s, 3H). Mass spectrum m/z 246.1 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. filtrationfiltered through a pad of Celite
  3. washthe solids were rinsed with EtOAc
  4. washThe filtrate was washed with water and brine
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (
  8. washeluting with a gradient from hexane to 90:10 hexane-EtOAc)

Sources & evidence

ORD record
ord-7553d0a4f97a4f52bf4f12aeb3b87bf2
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Reaction notes

Loading…