Reaction #2329071

Reaction equation

4-(2,2-dimethyl-2,3-dihydrobenzo[2,3-b]furan-7-yloxy)butan-1-ol

THF

sodium hydride

THF

1,2,3-trichloro-5-(phenylmethoxy)benzene

sodium chloride

→

subject compound

4-[2,3-dichloro-5-(phenylmethoxy)phenoxy}-2,2-dimethyl-2,3-dihydrobenzo[b]furan

Solvents

1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone

Conditions

Workup

1. 1
   workup.ADDITIONUpon completion of addition the reaction mixture
2. 2
   Temperatureto cool to ambient temperature
3. 3
   Concentrationit was concentrated under reduced pressure to a residue
4. 4
   workup.ADDITIONUpon completion of addition the reaction mixture
5. 5
   Temperaturewas heated to 130° C. where it
6. 6
   workup.STIRRINGwas stirred during an 18-hour period
7. 7
   TemperatureAfter this time the reaction mixture was cooled
8. 8
   Extractionit was extracted with three 25 mL portions of diethyl ether
9. 9
   WashThe combined extracts were washed with one 25 mL portion of water
10. 10
    Dryingdried with sodium sulfate
11. 11
    Filtrationfiltered
12. 12
    Concentrationthe filtrate was concentrated under reduced pressure to a residue
13. 13
    OtherThe residue was purified with column chromatography on silica gel using 25% methylene chloride in hexane and 50% methylene chloride in hexane as eluants
14. 14
    Concentrationconcentrated under reduced pressure

Procedure

Under a nitrogen atmosphere, a solution of 0.32 gram (0.008 mole) of 60% sodium hydride (in mineral oil) in 2 mL of THF was stirred and a solution of 1.65 grams (0.007 mole) of 4-(2,2-dimethyl-2,3-dihydrobenzo[2,3-b]furan-7-yloxy)butan-1-ol (Step B) in 10 mL of THF was added drop-wise. Upon completion of addition the reaction mixture was warmed to 40° C. where it stirred during a 15-minute period. After this time the reaction mixture was allowed to cool to ambient temperature and then it was concentrated under reduced pressure to a residue. To the residue was added a solution of 1.00 gram (0.0035 mole) of 1,2,3-trichloro-5-(phenylmethoxy)benzene (Step C) in 35 mL of 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone. Upon completion of addition the reaction mixture was heated to 130° C. where it was stirred during an 18-hour period. After this time the reaction mixture was cooled and stirred with 50 mL of an aqueous solution saturated with sodium chloride, then it was extracted with three 25 mL portions of diethyl ether. The combined extracts were washed with one 25 mL portion of water, dried with sodium sulfate, filtered, and the filtrate was concentrated under reduced pressure to a residue. The residue was purified with column chromatography on silica gel using 25% methylene chloride in hexane and 50% methylene chloride in hexane as eluants. The appropriate fractions were combined and concentrated under reduced pressure, yielding 0.54 gram of the subject compound. The NMR spectrum was consistent with the proposed structure.

Source