p-Toluenesulfonic acid → HCID 13720637, compound

HRID 1701905Notes

Reaction equation

HRID 1701905 reaction equation
CC(C)(O[CH2:6][CH2:7][CH2:8][CH:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)[OH:10])CC.C1(C)C=CC(S(O)(=O)=O)=CC=1.CNC(C1(C2C=CC=CN=2)CCCO1)=S>C1(C)C=CC=CC=1>[N:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[CH:9]1[CH2:8][CH2:7][CH2:6][O:10]1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 13043970HCID 13043970, compoundHCID 13720636HCID 13720636, compound

Product 1

HCID 13720637HCID 13720637, compoundYield 33.9%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
20 °C

Procedure

A solution of 4-(1,1-dimethylpropoxy)-1-(pyrid-2-yl)-butan-1-ol (122 g) and para-toluenesulphonic acid (107.4 g) in toluene (1000 cc) is kept at the boil for 28 hours so that the water formed is removed by azeotropic distillation. After cooling to a temperature of about 20° C., distilled water (250 cc) is added. The organic phase is decanted and washed with distilled water (50 cc); the aqueous phases are combined and neutralised by adding sodium bicarbonate (49 g). The mixture is extracted three times with ethyl acetate (1500 cc in total). The organic extracts are combined and filtered and the filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. A first oily fraction (30.8 g) is thus obtained. The aqueous phase previously obtained is re-extracted five times with methylene chloride (2500 cc in total); the organic extracts are combined, dried over anhydrous sodium sulphate and filtered and the filtrate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 35° C. A second oily fraction (11.2 g) is thus obtained. The two fractions (30.8 g and 11.2 g) are combined and run into polyphosphoric acid (200 g) at 80° C., in the course of 30 minutes. After stirring for 10 minutes at the same temperature and then cooling to a temperature of about 20° C., the reaction mixture is poured into distilled water (400 cc). A 10 N aqueous solution of sodium hydroxide (450 cc) is then added, whilst keeping the temperature below 20° C. The resulting crystals are filtered off and washed with ethyl acetate (500 cc). After separation of the filtrate by decantation, the aqueous phase is extracted three times with ethyl acetate (1500 cc in total). The organic extracts are combined, dried over anhydrous sodium sulphate and filtered and the filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C. 2-(Pyrid-2-yl)-tetrahydrofuran (26 g) is thus obtained.

Workup

  1. customformed
  2. customis removed by azeotropic distillation
  3. distillationdistilled water (250 cc)
  4. additionis added
  5. customThe organic phase is decanted
  6. washwashed with distilled water (50 cc)
  7. additionby adding sodium bicarbonate (49 g)
  8. extractionThe mixture is extracted three times with ethyl acetate (1500 cc in total)
  9. filtrationfiltered
  10. concentrationthe filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C
  11. customA first oily fraction (30.8 g) is thus obtained
  12. customThe aqueous phase previously obtained
  13. extractionis re-extracted five times with methylene chloride (2500 cc in total)
  14. dry with materialdried over anhydrous sodium sulphate
  15. filtrationfiltered
  16. concentrationthe filtrate is concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 35° C
  17. customA second oily fraction (11.2 g) is thus obtained
  18. temperaturecooling to a temperature of about 20° C.
  19. additionthe reaction mixture is poured
  20. distillationinto distilled water (400 cc)
  21. additionA 10 N aqueous solution of sodium hydroxide (450 cc) is then added
  22. customthe temperature below 20° C
  23. filtrationThe resulting crystals are filtered off
  24. washwashed with ethyl acetate (500 cc)
  25. customAfter separation of the filtrate by decantation
  26. extractionthe aqueous phase is extracted three times with ethyl acetate (1500 cc in total)
  27. dry with materialdried over anhydrous sodium sulphate
  28. filtrationfiltered
  29. concentrationthe filtrate is concentrated under reduced pressure (20 mm Hg; 2.7 kPa) at 40° C

Sources & evidence

ORD record
ord-8865f451200b44369c9b12bc2fdb1291
Source dataset
uspto-grants-1983_04
Patent number
US04379154

Reaction notes

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