Bromochloromethane → 2-(Chloromethoxy)-1,3-dimethylbenzene

HRID 1261380Notes

Reaction equation

HRID 1261380 reaction equation
[Cl:1][CH2:2][O:3][C:4]1[C:9]([CH3:10])=[CH:8][CH:7]=[CH:6][C:5]=1[CH3:11].[SH:12][CH2:13][CH2:14][C:15]([O:17]C)=[O:16].CC1C=CC=C(C)C=1O.[OH-].[Na+].BrCCl>O1CCCC1>[CH3:11][C:5]1[CH:6]=[CH:7][CH:8]=[C:9]([CH3:10])[C:4]=1[O:3][CH2:2][S:12][CH2:13][CH2:14][C:15]([OH:17])=[O:16].[Cl:1][CH2:2][O:3][C:4]1[C:5]([CH3:11])=[CH:6][CH:7]=[CH:8][C:9]=1[CH3:10]

Participants

8

Reactant 5

HCID 6333BromochloromethaneHCID 113352,6-DimethylphenolHCID 14798Sodium HydroxideHCID 18050Methyl 3-mercaptopropionateHCID 684883652-(Chloromethoxy)-1,3-dimethylbenzene2×

Product 2

HCID 593974173-[(2,6-Dimethylphenoxy)methylthio]propanoic acidHCID 684883652-(Chloromethoxy)-1,3-dimethylbenzeneYield 76%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
66 °C

Procedure

3-([2,6-Dimethylphenoxy]methylthio)propanoic acid 29 was prepared by reaction of 2-(chloromethoxy)-1,3-dimethylbenzene with methyl 3-mercaptopropanoate followed by hydrolysis of the ester. 2-(Chloromethoxy)-1,3-dimethylbenzene: A three-necked, 500-mL flask equipped with thermometer, reflux condenser, argon inlet, and a magnetic stirring bar was charged with 6.12 g (0.05 mol) of 2,6-dimethylphenol, 100 mL dry tetrahydrofuran, and 4.0 g (0.1 mol) sodium hydroxide powder. The mixture was heated at 66° C. for 1 hour. The mixture was cooled to room temperature, and 98 mL (1.5 mol) of bromochloromethane was added. The suspension that formed was cooled to room temperature, filtered through CELITE, and the solvent was removed under reduced pressure. The oily residue was purified by vacuum distillation (1-1.5 torr, b.p., 66° C.) to afford an overall yield of 6.50 g (76%) of 2-(chloromethoxy)-1,3-dimethylbenzene. 1H NMR (400 MHz, CDCl3): 2.33 (s, 6H), 5.80 (s, 2H), 6.99-7.06 (m, 3H).

Workup

  1. temperaturereflux condenser, argon inlet, and a magnetic stirring bar
  2. temperatureThe mixture was cooled to room temperature
  3. customThe suspension that formed
  4. temperaturewas cooled to room temperature
  5. filtrationfiltered through CELITE
  6. customthe solvent was removed under reduced pressure
  7. distillationThe oily residue was purified by vacuum distillation (1-1.5 torr, b.p., 66° C.)

Sources & evidence

ORD record
ord-e7ab6850eee54791af7ceed2656ea06e
Source dataset
uspto-grants-2013_06
Patent number
US08470861B2

Reaction notes

Loading…