Bromobenzene → 2-Fluoro-5-phenylamino-terephthalic Acid Dimethyl Ester

HRID 970327Notes

Reaction equation

HRID 970327 reaction equation
[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:13]=[C:12]([F:14])[C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][C:5]=1[NH2:15].Br[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1C=CC(P(C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1(C)C=CC=CC=1>[CH3:11][O:10][C:8](=[O:9])[C:7]1[CH:6]=[C:5]([NH:15][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:4]([C:3]([O:2][CH3:1])=[O:16])=[CH:13][C:12]=1[F:14]

Participants

7

Reactant 3

HCID 7961BromobenzeneHCID 10796Cesium carbonateHCID 16748146Dimethyl 2-amino-5-fluoroterephthalate

Product 1

HCID 167486382-Fluoro-5-phenylamino-terephthalic Acid Dimethyl EsterYield 80.2%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a mixture of 174B (10.0 g, 44.0 mmol), bromobenzene (4.6 mL, 44.0 mmol), (S)-(−)-2,2′-Bis(diphenylphosphino)-1,1′-binaphthyl (2.06 g, 3.30 mmol), and toluene (250 mL) was added cesium carbonate (20.0 g, 44.0 mmol) followed by palladium(II) acetate (0.494 g, 2.20 mmol). The mixture was heated at 90° C. for 24 h. HPLC indicated that the reaction was complete. The reaction mixture was cooled to room temperature, and filtered under reduced pressure through a pad of Celite topped with a pad of silica gel, and the Celite/Silica gel pad was rinsed with EtOAc. The filtrate was concentrated under reduced pressure and purified by silica gel chromatography using a 1:10 mixture of EtOAc and hexane to give 10.7 g (80%) of compound 174C as a pale yellow solid. HPLC retention time=3.72 min. (Condition A). 1H-NMR (400 MHz, CDCl3) δ 3.89 (s, 3H), 3.93 (s, 3H), 7.12 (m, 1H), 7.22 (m, 2H), 7.37 (m, 2H), 7.74 (m, 2H), and 9.22 (br s, 1H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered under reduced pressure through a pad of Celite
  3. washthe Celite/Silica gel pad was rinsed with EtOAc
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. custompurified by silica gel chromatography
  6. additiona 1:10 mixture of EtOAc and hexane

Sources & evidence

ORD record
ord-49b6917dfa0d409ba894878291e297dc
Source dataset
uspto-grants-2007_12
Patent number
US07312209B2

Reaction notes

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