Ammonia → Bromocriptine

HRID 1195076Notes

Reaction equation

HRID 1195076 reaction equation
C[Si](C)(C)[Br:3].[CH3:6][CH:7]([CH2:9][C@@H:10]1[N:19]2[C:20]([C@@:22]([NH:27][C:28]([C@@H:30]3[CH:45]=[C:44]4[C@@H:33]([CH2:34][C:35]5[C:39]6[C:40]4=[CH:41][CH:42]=[CH:43][C:38]=6[NH:37][CH:36]=5)[N:32]([CH3:46])[CH2:31]3)=[O:29])([CH:24]([CH3:26])[CH3:25])[O:23][C@@:18]2([OH:47])[C@H:17]2[N:13]([CH2:14][CH2:15][CH2:16]2)[C:11]1=[O:12])=[O:21])[CH3:8].N>CS(C)=O>[CH3:8][CH:7]([CH2:9][C@@H:10]1[N:19]2[C:20]([C@@:22]([NH:27][C:28]([C@@H:30]3[CH:45]=[C:44]4[C@@H:33]([CH2:34][C:35]5[C:39]6[C:38](=[CH:43][CH:42]=[CH:41][C:40]=64)[NH:37][C:36]=5[Br:3])[N:32]([CH3:46])[CH2:31]3)=[O:29])([CH:24]([CH3:25])[CH3:26])[O:23][C@@:18]2([OH:47])[C@H:17]2[N:13]([CH2:14][CH2:15][CH2:16]2)[C:11]1=[O:12])=[O:21])[CH3:6]

Participants

5

Reactant 3

HCID 222AmmoniaHCID 76113BromotrimethylsilaneHCID 134551Ergocryptine

Product 1

HCID 31101Bromocriptine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

1.3 ml of trimethylbromosilane (6 equivalents as calculated for α-ergocryptine to be brominated) are added to 40 ml of anhydrous dimethylsulfoxide and the solution is stirred at room temperature for 15 minutes. After adding 1 g (0.001739 mole) of α-ergocryptine, the mixture is stirred at room temperature for 10 minutes, then poured into 200 ml of ice-water and the pH value is adjusted to 8-9 by adding aqueous ammonia. The aqueous solution is extracted 3 times with 50 ml of dichloromethane each, then the combined organic phase is washed 3 times with 30 ml of 10% sodium chloride solution each. The dichloromethane solution is dried over anhydrous sodium sulfate, filtered and evaporated to 10 ml under reduced pressure. The residue is led through an aluminum oxide column moistened with 10 g of an 1:1 mixture of dichloromethane and ethyl acetate. The first fraction of 50 ml volume (containing the 2-bromo-α-ergocryptine) is evaporated to dryness, the residue is dissolved in 10 ml of dichloromethane, then 30 ml of diisopropyl ether are added to the residue and concentrated to its half volume under environmental pressure. The white crystalline precipitate is filtered off, washed and dried to give the title compound in a yield of 1.06 g (0.001617 mole, 93%), m.p.: 218° C., [α]D20 =-195° (c=1, dichloromethane).

Workup

  1. stirringthe mixture is stirred at room temperature for 10 minutes
  2. extractionThe aqueous solution is extracted 3 times with 50 ml of dichloromethane each, then the combined organic phase
  3. washis washed 3 times with 30 ml of 10% sodium chloride solution each
  4. dry with materialThe dichloromethane solution is dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. customevaporated to 10 ml under reduced pressure
  7. additionmoistened with 10 g of an 1:1 mixture of dichloromethane and ethyl acetate
  8. additionThe first fraction of 50 ml volume (containing the 2-bromo-α-ergocryptine)
  9. customis evaporated to dryness
  10. dissolutionthe residue is dissolved in 10 ml of dichloromethane
  11. addition30 ml of diisopropyl ether are added to the residue
  12. concentrationconcentrated to its half volume under environmental pressure
  13. filtrationThe white crystalline precipitate is filtered off
  14. washwashed
  15. customdried

Sources & evidence

ORD record
ord-570fce355927480897dbe7579413f69b
Source dataset
uspto-grants-1989_03
Patent number
US04816587

Reaction notes

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