Dimethyl Sulfate → 1-Chloro-2-methoxy-4-methylbenzene

HRID 1627340Notes

Reaction equation

HRID 1627340 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[OH:9].[CH3:10]OS(OC)(=O)=O.C([O-])([O-])=O.[K+].[K+]>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][C:3]=1[O:9][CH3:10]

Participants

4

Reactant 3

HCID 6497Dimethyl SulfateHCID 11430Potassium CarbonateHCID 120082-Chloro-5-methylphenol

Product 1

HCID 993521-Chloro-2-methoxy-4-methylbenzene

Procedure

To a solution of 2-chloro-5-methylphenol (10) (250 g, 1.75 mol) in CH3N (2.5 L) was added Me2SO4 (184 mL, 1.93 mol) and K2CO3 (314 g, 2.28 mol). The reaction mixture was heated to reflux for 6 h with mechanical stirring. The reaction mixture was cooled to ambient temperature and filtered through Celite. The filtrate was evaporated. The residue was diluted with EtOAc (1.5 L), washed with water (1.5 L*2) and brine (1.5 L) successively, dried over MgSO4, filtered and concentrated under reduced pressure to give 2-chloro-5-methylanisole (11) as a light yellow oil (274 g, quantitative). 1H NMR (400 MHz, CDCl3): δ 7.20-7.25 (d, 1H), 6.73 (s, 1H), 6.68-6.71 (d, 1H), 3.86 (s, 3H), 2.31 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 6 h with mechanical stirring
  3. filtrationfiltered through Celite
  4. customThe filtrate was evaporated
  5. additionThe residue was diluted with EtOAc (1.5 L)
  6. washwashed with water (1.5 L*2) and brine (1.5 L) successively
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-ed37a17d346849f2a901be85c3760209
Source dataset
uspto-grants-2014_07
Patent number
US08785488B2

Reaction notes

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