4-Methoxyphenylacetyl chloride → HCID 21107083, compound

HRID 1765394Notes

Reaction equation

HRID 1765394 reaction equation
[Cl-].[Al+3].[Cl-].[Cl-].C[O:6][C:7]1[CH:12]=[C:11]([F:13])[CH:10]=[C:9]([O:14][CH3:15])[CH:8]=1.[CH3:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25](Cl)=[O:26])=[CH:20][CH:19]=1>ClCCCl.ClC(Cl)C.[Cl-].[Zn+2].[Cl-]>[F:13][C:11]1[CH:10]=[C:9]([O:14][CH3:15])[CH:8]=[C:7]([OH:6])[C:12]=1[C:25](=[O:26])[CH2:24][C:21]1[CH:22]=[CH:23][C:18]([O:17][CH3:16])=[CH:19][CH:20]=1

Participants

7

Reactant 3

HCID 27346884-Methoxyphenylacetyl chlorideHCID 27742571-Fluoro-3,5-dimethoxybenzeneHCID 6451240Aluminum(III) Chloride

Product 1

HCID 21107083HCID 21107083, compound

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 111,2-DichloroethaneSolvent2×HCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
-10 °C

Procedure

To 1,2-dichloroethane (40 mL) were added anhydrous aluminum chloride (4.27 g) and zinc chloride (436 mg), followed by stirring 15 min. Under ice-cooling, a solution of 1,3-dimethoxy-5-fluorobenzene (5 g) in 1,2-dichloroethane (15 mL) was added. The mixture was cooled to −10° C. and 4-methoxyphenylacetyl chloride (4.9 mL) in dichloroethane (10 mL) was added drop-wise. The mixture was stirred 30 min at −10° C., and 1 h at room temperature and then heated to reflux for 2 h. The mixture was cooled at 0° C., poured carefully into ice-water and extracted twice with dichloromethane. The dichloromethane layer was dried over MgSO4 and evaporated in vacuo to give the title compound (9.1 g); 1H NMR (CDCl3): 13.23 (s, 1H), 7.17 (d, 2H, J=8.4 Hz), 6.88 (d, 2H, J=8.4 Hz), 6.24 (d, 1H, J=2.1 Hz), 6.18 (dd, 1H, J=13.8 Hz, J′=2.1 Hz), 4.20 (d, 2H, J=3.9 Hz), 3.82 (s, 3H), 3.80 (s, 3H); MS: 291 (MH+); containing 1-(4-fluoro-2-hydroxy-6-methoxyphenyl)-2-(4-methoxyphenyl)ethanone as a by-product. 1H NMR (CDCl3): 13.62 (s, 1H), 7.2–6.0 (6H), 4.29 (s, 2H), 3.90 (s, 3H), 3.81 (s, 3H).

Workup

  1. temperatureUnder ice-cooling
  2. stirringThe mixture was stirred 30 min at −10° C.
  3. temperature1 h at room temperature and then heated
  4. temperatureto reflux for 2 h
  5. temperatureThe mixture was cooled at 0° C.
  6. extractionextracted twice with dichloromethane
  7. dry with materialThe dichloromethane layer was dried over MgSO4
  8. customevaporated in vacuo

Sources & evidence

ORD record
ord-57e7c56d113548b9a52d78fe21a304ef
Source dataset
uspto-grants-2007_06
Patent number
US07226945B2

Reaction notes

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