Propofol → 2-(Chloromethoxy)-1,3-diisopropylbenzene

HRID 1765974Notes

Reaction equation

[CH:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([CH:10]([CH3:12])[CH3:11])[C:5]=1[OH:13])([CH3:3])[CH3:2].[OH-].[Na+].Br[CH2:17][Cl:18]>C1COCC1>[Cl:18][CH2:17][O:13][C:5]1[C:4]([CH:1]([CH3:3])[CH3:2])=[CH:9][CH:8]=[CH:7][C:6]=1[CH:10]([CH3:12])[CH3:11]

Participants

Conditions

Temperature: 62.5 °C

Procedure

A four-necked 500 mL round bottom flask was equipped with a mechanical stirrer, nitrogen inlet, condenser and thermometer. It was charged with 8.9 grams (0.05 moles) of 2,6-diisopropylphenol, 100 mL of THF and 4.0 grams (0.10 mole) of sodium hydroxide pellets. The resultant green suspension was heated to 60-65° C. and held for one hour. The reaction mixture was cooled to 30° C. and 100 mL (199 grams, 1.54 moles) bromochloromethane was added and heating was resumed. The reaction mixture was held at 64° C. for 2-3 hours until no more 2,6-diisopropylphenol was present as measured by GC. After cooling to 25° C., the suspension was filtered through Celite and the filter cake was washed with THF. The THF was removed by rotary evaporation and the resultant oil was distilled under vacuum (0-1 torr, b.p.=80° C.) to give 9.6 grams (0.042 moles, 85% yield) of O-chloromethyl 2,6-diisopropylphenol.

Workup

customA four-necked 500 mL round bottom flask was equipped with a mechanical stirrer, nitrogen inlet, condenser
temperatureThe reaction mixture was cooled to 30° C.
temperatureheating
temperatureAfter cooling to 25° C.
filtrationthe suspension was filtered through Celite
washthe filter cake was washed with THF
customThe THF was removed by rotary evaporation
distillationthe resultant oil was distilled under vacuum (0-1 torr, b.p.=80° C.)

Sources & evidence

ORD record: ord-5388dfe9aff847f5b22889dccd969ef1
Source dataset: uspto-grants-2007_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07229978B2

Reaction notes

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