4-Toluenesulfonyl chloride → 4-(2-Piperidinoethoxy)benzoic acid hydrochloride

HRID 1421370Notes

Reaction equation

HRID 1421370 reaction equation
C1(C)C=CC(S([Cl:10])(=O)=O)=CC=1.[N:12]1([CH:18](O)[CH3:19])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1.C(OCCCCC)(=O)C.C(=O)([O-])[O-].[K+].[K+].[OH:36][C:37]1[CH:46]=[CH:45][C:40]([C:41]([O:43]C)=[O:42])=[CH:39][CH:38]=1>C(Cl)Cl>[ClH:10].[N:12]1([CH2:18][CH2:19][O:36][C:37]2[CH:46]=[CH:45][C:40]([C:41]([OH:43])=[O:42])=[CH:39][CH:38]=2)[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1

Participants

7

Reactant 5

HCID 73974-Toluenesulfonyl chlorideHCID 7456MethylparabenHCID 11430Potassium CarbonateHCID 12348Amyl AcetateHCID 30305411-(Piperidin-1-yl)ethanol

Product 1

HCID 57438354-(2-Piperidinoethoxy)benzoic acid hydrochlorideYield 17.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
145 °C

Procedure

Into a 50 ml round bottom flask is placed 6.40 g (33.6 mmol) of p-toluenesulfonyl chloride and 25 ml of methylene chloride. The resulting solution is cooled with an ice bath as 4.00 g (31.0 mmol) of 1-piperidinoethanol in 6 ml of methylene chloride is added dropwise. After the addition is complete, the ice bath is removed and the resulting slurry is stirred for about 12 hours. The reaction mixture is concentrated on a rotary evaporator to yield a solid residue. The solid residue is transferred to a 100 ml round bottom flask with 45 ml of amyl acetate. Potassium carbonate (6.87 g, 49.7 mmol) and methyl 4-hydroxybenzoate (2.82 g, 18.5 mmol) are added to the slurry. The resulting mixture is heated to 145° C. for 2 hours. The reaction mixture is cooled to room temperature and washed twice with water. The organic layer is extracted with 11 ml of 8 N hydrochloric acid. The aqueous layer is heated at gentle reflux for 3 hours. The resulting slurry is cooled to 50° C. and 11 ml of acetone is added. The slurry is cooled to 0-5°0 C. and stirred for 1 hour. The product is filtered, washed with cold acetone, and dried at 50° C. in vacuo to yield 920 mg of product, (17%). 1H NMR. Potency 97.6%. TRS 1.16%

Workup

  1. customInto a 50 ml round bottom flask is placed
  2. additionis added dropwise
  3. additionAfter the addition
  4. customthe ice bath is removed
  5. concentrationThe reaction mixture is concentrated on a rotary evaporator
  6. customto yield a solid residue
  7. temperatureThe reaction mixture is cooled to room temperature
  8. washwashed twice with water
  9. extractionThe organic layer is extracted with 11 ml of 8 N hydrochloric acid
  10. temperatureThe aqueous layer is heated
  11. temperatureat gentle reflux for 3 hours
  12. temperatureThe resulting slurry is cooled to 50° C.
  13. addition11 ml of acetone is added
  14. temperatureThe slurry is cooled to 0-5°0 C
  15. stirringand stirred for 1 hour
  16. filtrationThe product is filtered
  17. washwashed with cold acetone
  18. customdried at 50° C. in vacuo

Sources & evidence

ORD record
ord-fdd0d51b2f09488a93c16e3493053966
Source dataset
uspto-grants-2000_06
Patent number
US06075146

Reaction notes

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