Hydrochloric Acid → 4-(3-((2-(1-Hydroxycyclohexyl)ethyl)-4-oxo-2-thiazolidinyl)propyl)benzoic acid

HRID 28206

Reaction equation

HRID 28206 reaction equation
O=[CH:2][CH2:3][CH2:4][CH2:5][C:6]1[CH:16]=[CH:15][C:9]([C:10]([O:12]CC)=[O:11])=[CH:8][CH:7]=1.[NH2:17][CH2:18][CH2:19][C:20]1([O:26]C2CCCCO2)[CH2:25][CH2:24][CH2:23][CH2:22][CH2:21]1.S([O-])([O-])(=O)=O.[Na+].[Na+].[SH:40][CH2:41][C:42](O)=[O:43].Cl>C(Cl)(Cl)(Cl)Cl.CO.O.C(Cl)(Cl)Cl>[OH:26][C:20]1([CH2:19][CH2:18][N:17]2[C:42](=[O:43])[CH2:41][S:40][CH:2]2[CH2:3][CH2:4][CH2:5][C:6]2[CH:7]=[CH:8][C:9]([C:10]([OH:12])=[O:11])=[CH:15][CH:16]=2)[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 1133Thioglycolic AcidHCID 24436Sodium SulfateHCID 128971821-Amino-2-[1-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]ethaneHCID 12897183Ethyl 4-(4-oxobutyl)benzoate

Product 1

HCID 1750274-(3-((2-(1-Hydroxycyclohexyl)ethyl)-4-oxo-2-thiazolidinyl)propyl)benzoic acidYield 32%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 5943Carbon TetrachlorideSolventHCID 6212ChloroformSolvent

Conditions

Temperature
25 °C

Procedure

Ethyl 4-(4-oxobutyl)benzoate (4.15 g., 18.8 mmol.) is added dropwise to a stirred solution of 1-amino-2-[1-(tetrahydro-2H-pyran-2-yloxy)cyclohexyl]ethane in carbon tetrachloride (1 ml.) maintained at 25° C. The resulting mixture is stirred for 30 minutes before being treated with anhydrous sodium sulfate (4 g.). Stirring is continued for 2 hours. The solid is removed by filtration and washed with a small quantity of benzene. The combined filtrate and washings are diluted with benzene (70 ml.), treated with HSCH2CO2H (1.84 g., 20 mmole.) in one portion, and then refluxed in a Dean-Stark apparatus for 16 hours. The reaction mixture is allowed to cool to room temperature, subsequently washed with diluted hydrochloric acid and 5% sodium bicarbonate, dried over anhydrous magnesium sulfate, and filtered. Evaporation in vacuo affords an oil residue which is dissolved in methanol (50 ml.) plus concentrated hydrochloric acid (0.2 ml.). The resulting mixture is stirred at ambient temperature for 3 hours, diluted with water, and extracted with ether. The ethereal extract is washed with diluted sodium bicarbonate, dried over anhydrous magnesium sulfate, filtered, and concentrated to give an oil residue. The oil residue is then applied to a silica gel column (120 g.) with chloroform. Elution with chloroform-methanol (100:1; v:v; 630 ml.) gives impure material. Further elution with the same eluant (300 ml.) provides the title compound (2.5 g., 5.96 mmol., 32%) as a pale yellow oil, pmr (CDCl3) δ1.38 (3H, t), 3.50 (2H, s), 4.40 (2H, q), 4.72 (1H, m), 7.23 (2 H, d), 8.00 (2H, d).

Workup

  1. stirringStirring
  2. waitis continued for 2 hours
  3. customThe solid is removed by filtration
  4. washwashed with a small quantity of benzene
  5. additionThe combined filtrate and washings are diluted with benzene (70 ml.)
  6. temperaturerefluxed in a Dean-Stark apparatus for 16 hours
  7. temperatureto cool to room temperature
  8. washsubsequently washed with diluted hydrochloric acid and 5% sodium bicarbonate
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customEvaporation in vacuo
  12. customaffords an oil residue which
  13. stirringThe resulting mixture is stirred at ambient temperature for 3 hours
  14. extractionextracted with ether
  15. extractionThe ethereal extract
  16. washis washed with diluted sodium bicarbonate
  17. dry with materialdried over anhydrous magnesium sulfate
  18. filtrationfiltered
  19. concentrationconcentrated
  20. customto give an oil residue
  21. washElution with chloroform-methanol (100:1; v:v; 630 ml.)
  22. customgives impure material
  23. washFurther elution with the same eluant (300 ml.)

Sources & evidence

ORD record
ord-52981b21eba84905a0d3ac01562ae02f
Source dataset
uspto-grants-1980_09
Patent number
US04225609

Linked notes

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