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Chemical Structure| 89407-97-6

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Product Details of [ 89407-97-6 ]

CAS No. :89407-97-6
Formula : C15H21NO3
M.W : 263.33
SMILES Code : O=C(OC)C1=CC=C(OCCN2CCCCC2)C=C1
MDL No. :MFCD21371820

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Application In Synthesis of [ 89407-97-6 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Downstream synthetic route of [ 89407-97-6 ]

[ 89407-97-6 ] Synthesis Path-Downstream   1~2

  • 1
  • [ 89407-97-6 ]
  • [ 84449-80-9 ]
YieldReaction ConditionsOperation in experiment
With hydrogenchloride; In acyl acetate; water; for 5 - 13h;Heating / reflux;Product distribution / selectivity; Example 1; Preparation of 4-(2-piperidinoethoxy)Benzoic Acid Hydrochloride; To a 2000 gallon reaction tank were added: 1320L of amyl acetate, 167.42 kg of methyl 4-hydroxybenzoate, 408.6 kg of anhydrous potassium carbonate, and 283.5 kg of beta-chloroethylpiperidine hydrochloride. The mixture was heated to 120° C.-125° C. for 5 hours, at which time HPLC analysis indicated complete consumption of the methyl 4-hydroxybenzoate. The tank was cooled to less than 50° C. 880 L of deionized water were added to the tank. The layers were separated and the aqueous layer was discarded. In a glass-lined tank was mixed 367 liters of food grade hydrochloric acid and 184 L of deionized water. The acid mixture was combined with the organic layer. The layers were separated and the organic layer was discarded. The mixture of the intermediate ester in aqueous acid heated to reflux until HPLC suggested no further consumption of the ester (13 hours). The mixture was cooled to less than 40° C., 550 liters of acetone was added to the mixture and the mixture was cooled to 0° C.-5° C. and stirred for 1 hour. The product was collected by filtration on a centrifuge. The wet cake was rinsed on the centrifuge with 400 L of acetone. The product was dried in a rotary vacuum (double cone) dryer at less than 50° C. and 25-27 inches in mercury. Yield was 91percent of theoretical. Example 2; Preparation of 4-(2-piperidinoethoxy)Benzoic Acid Hydrochloride; A 17.57 g portion of methyl 4-hydroxybenzoate and 132 mL of amyl acetate were combined. To this slurry at ambient temperature, was added 29.19 g of potassium carbonate sesquihydrate (particle size 96percent greater than 100 mesh, 100percent greater than 200 mesh) and 20.26 g of beta-chloroethylpiperidine hydrochloride. The mixture was heated to 110° C.-115° C. for 4.5 hours. The solution was cooled to less than 50° C. and 88 ml of deionized water were added. The layers were separated and the aqueous layer was discarded. To the organic phase was added 88 mL of deionized water the biphasic mixture stirred for 15 minutes and the phases separated. The aqueous phase was discarded. A dilute solution of aqueous hydrochloride acid was prepared by adding 42.6 g of reagent grade hydrochloric acid to 15 mL of deionized water. This solution was added to the organic phase, stirred for 15 minutes and the phases separated. The organic phase was discarded. The aqueous phase was heated to reflux for 5 hours. After approximately 1.5 hours at reflux the desired product began to precipitate. The product slurry was cooled to less than 40° C. and 55 mL of acetone was added. The mixture was cooled to 0° C.-5° C. and stirred for 1 hour. The product was collected by filtration and washed with a minimum of acetone pre-chilled to 0° C. The product was dried in a vacuum oven at ambient temperature. Yield was 90.6percent of theory. The potency of the product by HPLC compared to a reference standard was 99.2percent. Example 3; Preparation of 4-(2-piperidinoethoxy)Benzoic Acid Hydrochloride; A 17.57 g portion of methyl 4-hydroxybenzoate and 132 mL of amyl acetate were combined. To this slurry at ambient temperature, was added 29.19 g of powdered potassium carbonate (11percent water by Karl Fischer particle size not less than 95percent passing a 100 mesh sieve and not less than 90percent passing a 200 mesh sieve) and 20.26 g of beta-chloroethylpiperidine hydrochloride. The mixture was heated to 110° C.-115° C. for 4.5 hours. The solution was cooled to less than 50° C. and 88 mL of deionized water were added. The layers were separated and the aqueous layer was discarded. To the organic phase was added 88 mL of deionized water the biphasic mixture stirred for 15 minutes and the phases separated. The aqueous phase was discarded. A dilute solution of aqueous hydrochloride acid was prepared by adding 42.6 g of reagent grade hydrochloric acid to 15 mL of deionized water. This solution was added to the organic phase, stirred for 15 minutes and the phases separated. The organic phase was discarded. The aqueous phase was heated to reflux for 5 hours. After approximately 1.5 hours at reflux the desired product began to precipitate. The product slurry was cooled to less than 40° C. and 55 mL of acetone was added. The mixture was cooled to 0° C.-5° C. and stirred for 1 hour. The product was collected by filtration and washed with a minimum of acetone pre-chilled to 0° C. The product was dried in a vacuum oven at ambient temperature. Yield was 93.4percent of theory. The potency of the product by HPLC calibrated against a reference standard was 101.0percent. Example 4; Preparation of 4-(2-piperidinoethoxy)Benzoic Acid Hydrochloride; A 17.57 g portion of methyl 4-hydroxybenzoate and 132 mL of amyl acetate were combined. To this slurry at ambient temperature, was added 29.19 g of powdered potassium carbonate (11percent water by Karl Fischer particle size not less than 95percent passing a 100 mesh sieve and not less than 90percent passing ...
  • 2
  • [ 2008-75-5 ]
  • [ 99-76-3 ]
  • [ 89407-97-6 ]
  • [ 84449-80-9 ]
YieldReaction ConditionsOperation in experiment
95.3% With potassium carbonate; In Isopropyl acetate; water; a. To a 250 mL 3 neck flask, with mechanical stirring, condenser, and RTD probe were added the following under nitrogen atmosphere: 0.05 mol methyl 4-hydroxybenzoate, 0.06 mol beta-chloroethylpiperidine hydrochloride, 16.59 grams of potassium carbonate, and 60 mL of isopropyl acetate. The mixture was heated at 75° C.-80° C. for 20 hours, at which time all the methyl 4-hydroxybenzoate was consumed. 60 mL of water was then added to dissolve the potassium carbonate. The organic and aqueous phases were then Separated and the aqueous layer discarded. The organic layer was washed with a second 60 mL aliquot of water; the layers were separated and the aqueous layer discarded. The reaction product, 4-(2-piperidinoethoxy)benzoic acid, methyl ester, was then extracted into 25 mL 8N hydrochloric acid. The aqueous phase was separated and the organic phase discarded. The aqueous phase was refluxed in a 50 mL round bottomed flask with magnetic stirring and condenser for 48 hours. The mixture was then cooled to 0° C.-5° C. and the crystals removed by filtration. The crystals were rinsed with acetone and dried overnight in 50° C. vacuum oven. 13.63 g of 4-(2-piperidinoethoxy)benzoic acid hydrochloride were recovered, which is 95.3percent of the theoretical yield.
 

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