Boron trifluoride etherate → Lergotrile

HRID 866325Notes

Reaction equation

HRID 866325 reaction equation
[CH3:1][N:2]1[C@@H:7]2[CH2:8][C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[CH:15][C:16]=4[CH:6]2[CH2:5][C@@H:4]([CH2:18][C:19]#[N:20])[CH2:3]1)[NH:11][CH:10]=3.B(F)(F)F.CCOCC.C1C[C@H]2[C@@H](CC3C4C(=CC=CC2=4)NC=3)NC1.S(Cl)([Cl:49])(=O)=O>[OH-].[NH4+].C(Cl)Cl.C(#N)C>[CH3:1][N:2]1[C@@H:7]2[CH2:8][C:9]3[C:17]4[C:16](=[CH:15][CH:14]=[CH:13][C:12]=4[NH:11][C:10]=3[Cl:49])[C@H:6]2[CH2:5][C@@H:4]([CH2:18][C:19]#[N:20])[CH2:3]1

Participants

8

Reactant 4

HCID 8000Boron trifluoride etherateHCID 24648Sulfuryl chlorideHCID 15984218051-18-8HCID 6857537478-88-6

Product 1

HCID 6918447LergotrileYield 72%

Reagents, catalysts & solvents 3

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolventHCID 14923Ammonium HydroxideSolvent

Procedure

810 mg. of D-6-methyl-8-cyanomethylergoline were suspended in 50 ml. acetonitrile and the suspension cooled to -5° to 0° C. 1.25 ml. of boron trifluoride etherate were added thus solubilizing the ergoline. Next, a solution of 0.27 ml. of sulfuryl chloride in 20 ml. of methylene dichloride was added in dropwise fashion. The reaction mixture was stirred and cooled for 30 minutes, then diluted with ammonium hydroxide. The diluted solution was extracted with a chloroform-isopropanol 3:1 solvent mixture. The organic layer was separated, washed with a saturated aqueous sodium chloride solution, dried and the solvent evaporated. The residue comprising lergotrile formed in the above chlorination procedure was chromatographed over fluorosil using chloroform containing 2 percent methanol as the eluant; 660 mg. of lergotrile were obtained melting at 268°-271° C. (with decomposition), 72 percent yield.

Workup

  1. temperaturecooled for 30 minutes
  2. extractionThe diluted solution was extracted with a chloroform-isopropanol 3:1 solvent mixture
  3. customThe organic layer was separated
  4. washwashed with a saturated aqueous sodium chloride solution
  5. customdried
  6. customthe solvent evaporated
  7. customformed in the above chlorination procedure
  8. customwas chromatographed over fluorosil

Sources & evidence

ORD record
ord-4362f9172aa241a3b11896bbb8c319e4
Source dataset
uspto-grants-1978_07
Patent number
US04098790

Reaction notes

Loading…