2-Fluoroanisole → 4-(3-Fluoro-4-methoxy-benzoyl)-benzoic acid methyl ester

HRID 1716099

Reaction equation

HRID 1716099 reaction equation
[Al+3].[Cl-].[Cl-].[Cl-].[CH3:5][O:6][C:7](=[O:17])[C:8]1[CH:13]=[CH:12][C:11]([C:14](Cl)=[O:15])=[CH:10][CH:9]=1.[F:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[O:25][CH3:26]>ClCCl>[CH3:5][O:6][C:7](=[O:17])[C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:15])[C:23]2[CH:22]=[CH:21][C:20]([O:25][CH3:26])=[C:19]([F:18])[CH:24]=2)=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 675762-FluoroanisoleHCID 81850Methyl 4-(chlorocarbonyl)benzoateHCID 6451240Aluminum(III) Chloride

Product 1

HCID 686545474-(3-Fluoro-4-methoxy-benzoyl)-benzoic acid methyl esterYield 17.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To an ice-cooled slurry of AlCl3 (2.01 g, 15.1 mmol) in dichloromethane (10 mL) was slowly added 4-chlorocarbonyl-benzoic acid methyl ester (2 g, 10.1 mmol) in dichloromethane (5 mL). The reaction mixture was stirred for 20 min in the ice bath then 2-fluoroanisole (1.4 mL, 12.1 mmol) in dichloromethane (5 mL) was added. The reaction mixture was stirred at room temperature for 20 h. The reaction mixture was poured into ice cold 1 N HCl (10 mL) and the mixture was stirred for 15 min. The reaction mixture was transferred to a separatory funnel and the layers were separated. The aqueous layer was extracted with dichloromethane and the organic extracts were combined, washed with brine, dried over Na2SO4, filtered and concentrated. The crude solid was triturated with hot hexanes, filtered and washed with hexanes to give 0.5 g (17%) of compound 173 as a white powder. 1H NMR (400 MHz, DMSO-d6): δ 3.89 (s, 3H), 3.94 (s, 3H), 7.32 (t, J=8.5 Hz, 1H), 7.57 (d, J=8.8 Hz, 1H), 7.59-7.63 (m, 1H), 7.81 (d, J=8.2 Hz, 2H), 8.04 (s, 1H), 8.10 (d, J=8.3 Hz, 2H).

Workup

  1. stirringthe mixture was stirred for 15 min
  2. customThe reaction mixture was transferred to a separatory funnel
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with dichloromethane
  5. washwashed with brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude solid was triturated with hot hexanes
  10. filtrationfiltered
  11. washwashed with hexanes

Sources & evidence

ORD record
ord-cf9c27d8f88f4961879a418389856295
Source dataset
uspto-grants-2010_09
Patent number
US07799828B2

Linked notes

Loading…