Methyl iodide → HCID 18434164, compound

HRID 1636724Notes

Reaction equation

HRID 1636724 reaction equation
FC1C=CC=CC=1OC.C([Li])CCC.CN(C)CCN(C)CCN(C)C.CI.[Cl-].[Al+3].[Cl-].[Cl-].[Br:33][C:34]1[CH:42]=[CH:41][C:37]([C:38](Cl)=[O:39])=[CH:36][CH:35]=1.[F:43][C:44]1[C:49]([CH3:50])=[CH:48][CH:47]=[CH:46][C:45]=1[O:51][CH3:52]>C1COCC1.CCCCCC.[N+](C1C=CC=CC=1)([O-])=O>[Br:33][C:34]1[CH:42]=[CH:41][C:37]([C:38]([C:48]2[CH:47]=[CH:46][C:45]([O:51][CH3:52])=[C:44]([F:43])[C:49]=2[CH3:50])=[O:39])=[CH:36][CH:35]=1

Participants

11

Reactant 7

HCID 6328Methyl iodideHCID 18196PentamethyldiethylenetriamineHCID 675762-FluoroanisoleHCID 685154-Bromobenzoyl chlorideHCID 6451240Aluminum(III) ChlorideHCID 137069562-Fluoro-1-methoxy-3-methylbenzeneHCID 178418339Butyllithium

Product 1

HCID 18434164HCID 18434164, compound

Reagents, catalysts & solvents 3

HCID 7416NitrobenzeneSolvent2×HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-78 °C

Procedure

Aa) A solution of 5.6 ml of 2-fluoroanisole in 60 ml of absolute THF is cooled to -78° C. and treated within 15 min. with 31.3 ml of 1.6M butyllithium in hexane. After 15 min. 8.7 g of 1,1,4,7,7-pentamethyldiethylenetriamine are added dropwise and, after a further 2 hrs. at -78° C., 9.4 ml of methyl iodide are added dropwise. The mixture is stirred at -78° C. overnight, then evaporated and taken up in ether/1N hydrochloric acid. The aqueous phase is extracted with ether and the organic phase is dried over sodium sulphate and evaporated in order to give crude 2-fluoro-3-methyl-anisole. 30 ml of nitrobenzene are cooled in an ice bath and then treated in succession with 8.1 g of aluminium chloride and 11.9 g of 4-bromobenzoyl chloride in 9 ml of nitrobenzene at a maximum 6° C. The mixture is stirred and then the 2-fluoro-3-methyl-anisole is added in such a manner that the temperature does not rise above 6° C. The solution is left to warm to room temperature overnight, poured into ice-water/ ethyl acetate and washed with 10% aqueous sodium chloride solution, dried and concentrated. After chromatography over silica gel with hexane/ether (95/5) as the eluent and crystallization from hexane there are obtained 4.0 g of (4-bromo-phenyl)-(3-fluoro-4-methoxy-2-methyl-phenyl)-methanone, m.p. 93-95° C.

Workup

  1. customevaporated
  2. extractionThe aqueous phase is extracted with ether
  3. dry with materialthe organic phase is dried over sodium sulphate
  4. customevaporated in order
  5. customto give crude 2-fluoro-3-methyl-anisole
  6. stirringThe mixture is stirred
  7. customdoes not rise above 6° C
  8. waitThe solution is left
  9. temperatureto warm to room temperature overnight
  10. washwashed with 10% aqueous sodium chloride solution
  11. customdried
  12. concentrationconcentrated
  13. customAfter chromatography over silica gel with hexane/ether (95/5) as the eluent and crystallization from hexane

Sources & evidence

ORD record
ord-a48111d09b6544f5884a444b28792f1d
Source dataset
uspto-grants-2000_03
Patent number
US06034275

Reaction notes

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