1-(2-Bromoethyl)-4-chlorobenzene

Pale yellow oil

The volume efficiency was 1.76 L per Kg of 2-(4'-chlorophenyl)ethanol starting material or 758 g of 2-(4'-chlorophenyl)ethyl bromide product (assay corrected) per liter.Process DescriptionTo a reactor affixed with a vent to a caustic scrubber to capture HBr gas that might evolve during the reaction was added 2-(4'-chlorophenyl)ethanol (1.00 Kg, 6.39 moles, 1.00 equiv.). The reactor contents were cooled to 0° C. The feed pump and line were rinsed with cyclohexane (0.019 Kg), and the rinses were directed to waste disposal. To the cooled solution was added phosphorous tribromide (0.869 Kg, 3.21 moles, 0.503 equiv.) while the stirred reactor contents were maintained at 0-10° C. The resulting reaction was highly exothermic and was controlled by the addition rate with a jacket temperature of -5° C. to -10° C. The feed pump and line was rinsed with cyclohexane (0.019 Kg), and the rinses were directed to waste disposal. The resulting reaction mixture was heated to 25° C. (20° C. to 30° C.), and stirring was continued at this temperature for 2 hours (1 to 3 hours). After this time, the reaction mixture was slowly heated to 80° C. (75 to 85° C.) over 60 minutes (45 to 75 minutes), and stirring at that temperature was continued for 3 hours (2 to 4 hours). A slightly turbid emulsion was formed upon heating. The reactor contents were cooled to 22° C. and then a sample of the reaction mixture was analyzed for reaction completion (>99percent by HPLC peak area). The reaction mixture was a thick but easily stirred emulsion. A receiver vented to a caustic scrubber was charged with purified water (0.514 Kg). The receiver contents were cooled to 5-20° C. The reaction mixture was transferred from the reactor to the receiver at a rate sufficiently slow to maintain the stirred receiver contents at about 15° C. The receiver contents were warmed to 35-40° C. and filtered through a polishing filter. The reactor was washed with additional purified water (0.085 Kg), and the washings were passed through the filter into the aqueous product mixture. The phases were allowed to separate at 35-40° C. The lower phase was drained from the upper phase. The lower phase weighed about 1.39 Kg and was about 96percent pure 2-(4'-chlorophenyl)ethyl bromide, which was therefore obtained in about 94.9percent yield (assay corrected).The present invention uses SM-A and LCS-1 condensation to prepare Impurity F.Specific operations are as follows: 40g of p-chlorophenylacetic acid was added to 400ml of tetrahydrofuran, Stirring at room temperature dissolved; lithium aluminum hydride in batches, temperature control at 25 ~ 30 , After the reaction was stirred for 20 hours, 200 ml of water was added slowly and the addition was completed.Add ethyl acetate 400ml stirred 30min, liquid separation, organic phase plus 200ml saturated brine and dried over 20g anhydrous sodium sulfate, filtered, the filtrate was concentrated under reduced pressure 40 ~ 45 , 36.7 g of oil (S2) was obtained; S2 was added to the reaction flask, the temperature was lowered to 0 to 5 ° C in ice water, Slowly dropping phosphorus tribromide, dropping temperature during the course of 0 ~ 5 , the dropwise addition is completed, Heated to 25 ~ 30 , incubated for 3h, Add water 80ml, stirred 30min, liquid separation, the aqueous phase was extracted with dichloromethane 100ml × 2, The organic phases were combined and concentrated under reduced pressure to give an oil (S3): 48.8 g. Yield: 94.9percent.EXAMPLE 5

Molecular Weight:219.50
XLogP3:3.7
Rotatable Bond Count:2
Exact Mass:217.94979
Monoisotopic Mass:217.94979
Heavy Atom Count:10
Complexity:87.3
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes