Triethylamine → HCID 13621772, compound

HRID 746095Notes

Reaction equation

HRID 746095 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][N:13]2[CH:17]=[C:16]([CH2:18][O:19][C:20]3[CH:25]=[CH:24][C:23]([CH2:26][OH:27])=[CH:22][CH:21]=3)[O:15]C2=O)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].CCN(CC)CC.CS(Cl)(=O)=O.C([O-])([O-])=O.[K+].[K+].O[CH2:48][C:49]1[N:50](C(C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[CH:51]=[CH:52][N:53]=1.[H-].[Na+]>C(Cl)Cl.O.CS(C)=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:11][CH2:12][NH:13][CH2:17][CH:16]([OH:15])[CH2:18][O:19][C:20]2[CH:21]=[CH:22][C:23]([CH2:26][O:27][CH2:48][C:49]3[NH:50][CH:51]=[CH:52][N:53]=3)=[CH:24][CH:25]=2)[CH:6]=[CH:7][C:8]=1[O:9][CH3:10]

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 24758Sodium hydride2×HCID 31297Methanesulfonyl chloride2×HCID 11131622HCID 11131622, compoundHCID 53968850HCID 53968850, compound

Product 1

HCID 13621772HCID 13621772, compoundYield 13%

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

Compound XXXI (2.71 g, 0.007 mL) was dissolved in CH2Cl2 (25 mL), cooled and Et3N (0.78 g, 0.0077 mol) added. To the cooled solution, methanesulfonyl chloride (0.88 g, 0.0077 mol) in CH2Cl2 (2 mL) was added and stirred at room temperature. After 3 hours another portion of methanesulfonylchloride (0.09 g, 0.007 mol) was added. After 1 hour, the reaction was poured in H2O (25 mL) containing K2CO3 (1 g) and the organic extracted with CH2Cl2 (3X). The aqueous extracts were washed with H2O, 0.5N, HCl, H2O, dried, filtered and concentrated to dryness. The residue was dissolved in dry DMSO (20 mL) and added with stirring at room temperature to a solution of XXX (1.7 g, 0.005 mol) and NaH (60% oil dispersion, 0.22 g, 0.0055 mol) in DMSO (20 mL). After 2 hours, another portion of NaH (0.2 g) was added and stirred at room temperature for an additional 2 hours. The solution was then poured in H2O and the aqueous extracted with EtOAc (2X). The organic extracts were dried, filtered and concentrated to dryness. The residue was treated with CH3OH (25 mL) and 40% NaOH (6 mL) and the solution heated at reflux. After 2 hours, the solution was poured into H2O. The aqueous layer was extracted with CHCl3 (3X) and the organic extracts dried, filtered and concentrated to dryness. The residue was treated with CH3OH (50 mL) and HOAc (2.5 mL) and heated at reflux for 2 hours. The reaction was then concentrated to dryness, 0.1N HCl (75 mL) added, the aqueous extracted with CHCl3 (3X) and the organic extracts discarded. The aqueous solution was basified to pH 10 with saturated Na2CO3 and extracted with CHCl3 (2X). The organic extracts were dried, filtered and concentrated to dryness. The residue was chromatographed on silica gel eluting with CHCl3 saturated with NH3 and CHCl3 --CH3OH--NH4OH (70:5:0.5 to 90:10:1) to yield XXXII; 13% yield.

Workup

  1. temperaturecooled
  2. extractionthe organic extracted with CH2Cl2 (3X)
  3. washThe aqueous extracts were washed with H2O, 0.5N, HCl, H2O
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. dissolutionThe residue was dissolved in dry DMSO (20 mL)
  8. additionadded
  9. waitAfter 2 hours
  10. stirringstirred at room temperature for an additional 2 hours
  11. extractionthe aqueous extracted with EtOAc (2X)
  12. customThe organic extracts were dried
  13. filtrationfiltered
  14. concentrationconcentrated to dryness
  15. additionThe residue was treated with CH3OH (25 mL) and 40% NaOH (6 mL)
  16. temperaturethe solution heated
  17. temperatureat reflux
  18. waitAfter 2 hours
  19. additionthe solution was poured into H2O
  20. extractionThe aqueous layer was extracted with CHCl3 (3X)
  21. customthe organic extracts dried
  22. filtrationfiltered
  23. concentrationconcentrated to dryness
  24. additionThe residue was treated with CH3OH (50 mL) and HOAc (2.5 mL)
  25. temperatureheated
  26. temperatureat reflux for 2 hours
  27. concentrationThe reaction was then concentrated to dryness, 0.1N HCl (75 mL)
  28. additionadded
  29. extractionthe aqueous extracted with CHCl3 (3X)
  30. extractionextracted with CHCl3 (2X)
  31. customThe organic extracts were dried
  32. filtrationfiltered
  33. concentrationconcentrated to dryness
  34. customThe residue was chromatographed on silica gel eluting with CHCl3 saturated with NH3 and CHCl3 --CH3OH--NH4OH (70:5:0.5 to 90:10:1)

Sources & evidence

ORD record
ord-b13e82baa5d04d74aacbe4f9936b0420
Source dataset
uspto-grants-1986_07
Patent number
US04602093

Reaction notes

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