Methanol → HCID 20190400, compound

HRID 1788767Notes

Reaction equation

HRID 1788767 reaction equation
S([CH2:11][N+:12]#[C-])(C1C=CC(C)=CC=1)(=O)=O.CC([O-])(C)C.[K+].[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]2[N:30]3[CH2:31][S:32][CH2:33][C:29]3=[C:28]([CH:34]=O)[CH:27]=2)[CH:21]=1.CO>COCCOC>[N:20]1[CH:25]=[CH:24][CH:23]=[C:22]([C:26]2[N:30]3[CH2:31][S:32][CH2:33][C:29]3=[C:28]([CH2:34][C:11]#[N:12])[CH:27]=2)[CH:21]=1

Participants

6

Reactant 4

HCID 887MethanolHCID 161915Tosylmethyl isocyanideHCID 14150480HCID 14150480, compoundHCID 23665647Potassium tert-butoxide

Product 1

HCID 20190400HCID 20190400, compoundYield 71.6%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent3×

Conditions

Temperature
-30 °C

Procedure

A solution of tosylmethyl isocyanide (7.5 g) in 1,2-dimethoxyethane (50 cc) is added over 20 minutes at a temperature of about -30° C. to a solution of potassium tert-butylate (8.7 g) in 1,2-dimethoxyethane (140 cc) cooled to a temperature of about -30° C. The solution obtained is cooled to a temperature of about -60° C., and then a solution of 5-(3-pyridyl)-1H,3H-pyrrolo[1,2-c]thiazole-7-carboxaldehyde (8 g) in 1,2-dimethoxyethane (70 cc) is added to it over 30 minutes at a temperature of about -60° C. The solution obtained is brought to a temperature of about 0° C. over 1 hour and then kept at this temperature for 1 hour and 20 minutes. Methanol (105 cc) is then added over 15 minutes, at a temperature of between 3 and 7° C. The solution obtained is heated at a temperature of about 72° C. for 1 hour and 15 minutes and is then stirred at a temperature of about 20° C. for 16 hours. Three-quarters of the solvent are evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 40° C. The residue is taken up with a mixture of distilled water (350 cc) and ethyl acetate (250 cc). The organic phase is separated off and the aqueous phase is extracted 3 times with ethyl acetate (750 cc in total). The organic extracts are combined, washed 3 times with distilled water (450 cc in total), dried over anhydrous magnesium sulphate, treated with decolourising charcoal (0.5 g), filtered and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 50° C. A crude product (7.6 g) is thus obtained. This product is chromatographed on a 2.7 cm diameter column containing silica (0.063-0.2 mm; 75 g) by eluting with mixtures of cyclohexane and ethyl acetate and collecting 200-cc fractions. The first 2 fractions from the elution with a mixture of cyclohexane and ethyl acetate (50:50 by volume) are rejected. The next 3 fractions from the elution with a mixture of cyclohexane and ethyl acetate (50:50 by volume) and the following fraction from the elution with pure ethyl acetate, are combined and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 60° C. 2-[-5-(3-Pyridyl)-1H,3H-pyrrolo[1,2-c]thiazol-7-yl]acetonitrile (6 g) is thus obtained in the form of light yellow crystals melting at 92° C.

Workup

  1. customThe solution obtained
  2. temperatureis cooled to a temperature of about -60° C.
  3. customThe solution obtained
  4. waitkept at this temperature for 1 hour and 20 minutes
  5. customThe solution obtained
  6. temperatureis heated at a temperature of about 72° C. for 1 hour and 15 minutes
  7. customThree-quarters of the solvent are evaporated off under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 40° C
  8. additionThe residue is taken up with a mixture of distilled water (350 cc) and ethyl acetate (250 cc)
  9. customThe organic phase is separated off
  10. extractionthe aqueous phase is extracted 3 times with ethyl acetate (750 cc in total)
  11. washwashed 3 times with distilled water (450 cc in total)
  12. dry with materialdried over anhydrous magnesium sulphate
  13. additiontreated with decolourising charcoal (0.5 g)
  14. filtrationfiltered
  15. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 50° C
  16. customA crude product (7.6 g) is thus obtained
  17. customThis product is chromatographed on a 2.7 cm diameter column
  18. additioncontaining silica (0.063-0.2 mm; 75 g)
  19. washby eluting with mixtures of cyclohexane and ethyl acetate
  20. customcollecting 200-cc fractions
  21. washThe first 2 fractions from the elution
  22. additionwith a mixture of cyclohexane and ethyl acetate (50:50 by volume)
  23. washThe next 3 fractions from the elution
  24. additionwith a mixture of cyclohexane and ethyl acetate (50:50 by volume)
  25. washthe following fraction from the elution with pure ethyl acetate
  26. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at a temperature of about 60° C

Sources & evidence

ORD record
ord-e9a3504efdb64c92b1aeea28125c9957
Source dataset
uspto-grants-1987_08
Patent number
US04684658

Reaction notes

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