Methane → HCID 13711421, compound

HRID 2118725Notes

Reaction equation

HRID 2118725 reaction equation
C([Li])CCC.ClCCC[CH:10]([O:18][CH:19]([C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=1)[CH2:20][CH2:21]CCl)C1C=CC=C(C)N=1.[CH3:31][N:32]=[C:33]=[S:34].C>CCCCCC.C(O)C.CN(P(N(C)C)(N(C)C)=O)C.O1CCCC1>[CH3:31][NH:32][C:33]([C:19]1([C:24]2[CH:29]=[CH:28][CH:27]=[C:26]([CH3:30])[N:25]=2)[CH2:20][CH2:21][CH2:10][O:18]1)=[S:34]

Participants

9

Reactant 4

HCID 297MethaneHCID 11167Methyl isothiocyanateHCID 56625968HCID 56625968, compoundHCID 178418339Butyllithium

Product 1

HCID 13711421HCID 13711421, compoundYield 49.3%

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent3×HCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent3×

Procedure

To a 1.6M solution (3,150 cc) of n-butyllithium in hexane maintained under an atmosphere of nitrogen at between -65° and -70° C., a mixture (1,680 cc) of anhydrous tetrahydrofuran and anhydrous hexamethylphosphorotriamide (50:50 by volume) is added slowly, followed by a solution of 3-chloropropyl(6-methyl-2-pyridyl)methyl ether (360 g) in a mixture (1,080 cc) of anhydrous tetrahydrofuran and anhydrous hexamethylphosphorotriamide (50:50 by volume) added dropwise in the course of 1 hour. After 5 minutes' stirring, a solution of methyl isothiocyanate (158 g) in a mixture (432 cc) of anhydrous tetrahydrofuran and anhydrous hexamethylphosphorotriamide (50:50 by volume) is added in the course of 35 minutes. The mixture is stirred for 1 hour at -60° C. and distilled water (4,800 cc) is then added slowly, the temperature being allowed to rise to about 20° C. The mixture is stirred for 5 minutes and then extracted with ethyl acetate (2,400 cc). The aqueous phase is decanted and extracted 4 times with ethyl acetate (6,000 cc in total). The organic liquors are combined, washed twice with aqueous sodium chloride solution (1,800 cc in total) at a concentration of 180 g per liter, and then extracted 3 times with 2N aqueous hydrochloric acid solution (4,500 cc in total). The acidic aqueous extracts are combined, washed twice with diethyl ether (3,000 cc in total) and then brought to a pH in the region of 8 using 10N aqueous sodium hydroxide solution. The mixture is extracted 4 times with ethyl acetate (10 liters in total). The organic extracts are combined, washed twice with distilled water (3.6 liters in total), dried over anhydrous magnesium sulphate in the presence of decolorising charcoal (18 g) for 1 hour and then filtered. The filtrate is concentrated to a small volume under reduced pressure (30 mm Hg; 4 kPa) at a temperature in the region of 35° C. The crystallised product is separated by filtration, washed with isopropanol (180 cc) and dried in a stream of air. The product obtained (118 g) is dissolved in boiling absolute ethanol (472 cc). To the solution is added decolorising charcoal (1 g), and the mixture is filtered hot. The filter is washed with a little boiling ethanol, and the solution is then cooled in an ice bath for 1 hour. The crystals which appear are separated by filtration, washed with ice-cooled absolute ethanol (120 cc) and dried in a stream of air at 20° C. N-Methyl-2-(6-methyl-2-pyridyl)-2-tetrahydrofurancarbothioamide (110 g), m.p. 151.4° C., is thereby obtained.

Workup

  1. additionadded dropwise in the course of 1 hour
  2. stirringThe mixture is stirred for 1 hour at -60° C.
  3. distillationdistilled water (4,800 cc)
  4. additionis then added slowly
  5. customto rise to about 20° C
  6. stirringThe mixture is stirred for 5 minutes
  7. extractionextracted with ethyl acetate (2,400 cc)
  8. customThe aqueous phase is decanted
  9. extractionextracted 4 times with ethyl acetate (6,000 cc in total)
  10. washwashed twice with aqueous sodium chloride solution (1,800 cc in total) at a concentration of 180 g per liter
  11. extractionextracted 3 times with 2N aqueous hydrochloric acid solution (4,500 cc in total)
  12. washwashed twice with diethyl ether (3,000 cc in total)
  13. extractionThe mixture is extracted 4 times with ethyl acetate (10 liters in total)
  14. washwashed twice with distilled water (3.6 liters in total)
  15. dry with materialdried over anhydrous magnesium sulphate in the presence of decolorising charcoal (18 g) for 1 hour
  16. filtrationfiltered
  17. concentrationThe filtrate is concentrated to a small volume under reduced pressure (30 mm Hg; 4 kPa) at a temperature in the region of 35° C
  18. customThe crystallised product is separated by filtration
  19. washwashed with isopropanol (180 cc)
  20. customdried in a stream of air
  21. customThe product obtained (118 g)
  22. dissolutionis dissolved
  23. additionTo the solution is added
  24. filtrationthe mixture is filtered hot
  25. washThe filter is washed with
  26. temperaturethe solution is then cooled in an ice bath for 1 hour
  27. customThe crystals which appear are separated by filtration
  28. washwashed with ice-
  29. temperaturecooled absolute ethanol (120 cc)
  30. customdried in a stream of air at 20° C

Sources & evidence

ORD record
ord-84495c7ab5ca4c9fa9ca0e40deaf8597
Source dataset
uspto-grants-1987_07
Patent number
US04680303

Reaction notes

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