Chloromethyl Methyl Ether → 1-BROMO-4-(METHOXYMETHOXY)-2-METHYLBENZENE

To a solution of 4-bromo-3-methylphenol (6-6) (1.0 equiv.) in DMF (0.5 M) at 0° C. was added portionwise 60% wt NaH (1.5 equiv.). The addition was controlled such that internal reaction temperature never went above 10° C. The reaction was stirred at room temperature for 45 minutes, then a solution of chloro(methoxy)methane (1.2 equiv.) in DMF (3 M) was added dropwise via additional funnel. The reaction was stirred at room temperature for 3.5 hours, and then quenched by pouring into ice. The resulting mixture was stirred at room temperature for 1 hour. Ether was added, and the two layers were separated. The aqueous layer was extracted (1×) with ether. The combined organic layers were washed with water (2×), brine, dried over MgSO4, and concentrated to give 1-bromo-4-(methoxymethoxy)-2-methylbenzene (6-7) as a colorless oil. The crude material was used in the next step without further purification.

1. additionThe addition
2. customwas controlled such that internal reaction temperature never went above 10° C
3. stirringThe reaction was stirred at room temperature for 3.5 hours
4. customquenched
5. additionby pouring into ice
6. stirringThe resulting mixture was stirred at room temperature for 1 hour
7. additionEther was added
8. customthe two layers were separated
9. extractionThe aqueous layer was extracted (1×) with ether
10. washThe combined organic layers were washed with water (2×), brine
11. dry with materialdried over MgSO4
12. concentrationconcentrated

ORD record

ord-3bcc542d14f14a2dab7ee2d33c7b8fed

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09045470B2