Iodine → HCID 19422450, compound

HRID 374566Notes

Reaction equation

HRID 374566 reaction equation
[CH2:1]([CH:3]1[O:5][CH2:4]1)Cl.[CH3:6][NH:7][CH2:8][C:9]#[CH:10].[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.[K].II>CO.ClCCl.CO.CCCCCC.C1COCC1.N1C=CC=CC=1>[OH:5][CH:3]([CH2:4][N:7]([CH3:6])[CH2:8][C:9]#[CH:10])[CH2:1][N:15]1[C:11](=[O:21])[C:12]2[C:13](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:14]1=[O:16]

Participants

9

Reactant 4

HCID 807IodineHCID 7835EpichlorohydrinHCID 96160N-methylpropyn-2-ylamineHCID 24194345Phthalimide potassium salt

Product 1

HCID 19422450HCID 19422450, compoundYield 41.1%

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 1049PyridineSolventHCID 21226129Dichloromethane methanolSolventHCID 21883165Tetrahydrofuran hexaneSolvent

Procedure

A mixture of epichlorohydrin (6.03 g, 5.1 ml, 0.065 mole), 0.1 ml of pyridine and N-methyl-N-propargylamine (4.095 g, 0.059 ml, 0.059 mole) in 15 ml of anhydrous methanol was stirred for 2 hours at 40°-45° C. After stirring overnight at ambient temperature, the TLC (hexane-THF 6:4, UV) showed that the starting amine was practically consumed. The solvent was evaporated and the crude product dissolved in 50 ml of anhydrous DMF. Potassium phthalimide (12.57 g, 0.068 mole) was added and the mixture refluxed for 8 hours. TLC (dichloromethane/methanol 95:5, UV, I2) showed formation of a new product with Rf 0.26. The mixture was filtered cold and the flitrate diluted with 30{) ml of EtOAc. The solution was washed with water (10×200 ml), brine (1×200m ml) and dried (MgSO4). After removal of the solvent, the residue was preabsorbed on Merck silica gel-60 and purified by flash chromatography (step gradient from 0 to 5% methanol in dichloromethane). The pure fractions were combined, evaporated and dried in vacuo to yield an off white solid (6.6 g).

Workup

  1. stirringAfter stirring overnight at ambient temperature
  2. customwas practically consumed
  3. customThe solvent was evaporated
  4. dissolutionthe crude product dissolved in 50 ml of anhydrous DMF
  5. temperaturethe mixture refluxed for 8 hours
  6. filtrationThe mixture was filtered cold
  7. additionthe flitrate diluted with 30{) ml of EtOAc
  8. washThe solution was washed with water (10×200 ml), brine (1×200m ml)
  9. dry with materialdried (MgSO4)
  10. customAfter removal of the solvent
  11. customthe residue was preabsorbed on Merck silica gel-60
  12. custompurified by flash chromatography (step gradient from 0 to 5% methanol in dichloromethane)
  13. customevaporated
  14. customdried in vacuo

Sources & evidence

ORD record
ord-500806d8aa7249539277c21dd9a77af1
Source dataset
uspto-grants-1996_01
Patent number
US05480988

Reaction notes

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