Ethyl Acetate → 8alpha-(3,3-Diethylureido)-6-methylergoline-2-carboxylic acid benzyl ester

HRID 569320Notes

Reaction equation

HRID 569320 reaction equation
I[C:2]1[NH:16][C:15]2[C:17]3[C:3]=1[CH2:4][C@@H:5]1[C@@H:10]([C:11]=3[CH:12]=[CH:13][CH:14]=2)[CH2:9][C@H:8]([NH:18][C:19](=[O:25])[N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])[CH2:7][N:6]1[CH3:26].[C:27]([O:30][CH2:31][CH3:32])(=[O:29])C>C(O)C1C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:31]([O:30][C:27]([C:2]1[NH:16][C:15]2[C:17]3[C:3]=1[CH2:4][C@@H:5]1[C@@H:10]([C:11]=3[CH:12]=[CH:13][CH:14]=2)[CH2:9][C@H:8]([NH:18][C:19]([N:20]([CH2:23][CH3:24])[CH2:21][CH3:22])=[O:25])[CH2:7][N:6]1[CH3:26])=[O:29])[C:32]1[CH:11]=[CH:17][CH:3]=[CH:4][CH:5]=1

Participants

5

Reactant 2

HCID 8857Ethyl AcetateHCID 135590301,1-Diethyl-3-(2-iodo-6-methyl-8alpha-ergolinyl)urea

Product 1

HCID 135590328alpha-(3,3-Diethylureido)-6-methylergoline-2-carboxylic acid benzyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 244Benzyl AlcoholSolvent

Procedure

300 mg (0.644 mmol) of 3-(2-iodo-6-methyl-8α-ergolinyl)-1,1-diethylurea is heated, after adding 0.169 ml (0.709 mmol) of tri-m-butylamine, in 4 ml of benzyl alcohol, combined under a carbon monoxide atmosphere with 7 mg (0.031 mmol) of palladium(II) acetate, and kept at 100°-110° C. for 2.5 hours under vigorous agitation. After cooling to room temperature, the reaction solution is diluted with ethyl acetate and extracted with saturated sodium bicarbonate solution and saturated sodium chloride solution. After drying over magnesium sulfate, the ethyl acetate is removed by distillation under reduced pressure and then the benzyl alcohol is distilled off under a high vacuum. By column chromatography on 150 g of silica gel in a system of dichloromethane/ethanol=10:1 and recrystallization from ethanol/hexane, 166 mg of 8α-(3,3-diethylureido)-6-methylergoline-2-carboxylic acid benzyl ester is produced from the crude product (54.5%), mp 226°-229° C.

Workup

  1. extractionextracted with saturated sodium bicarbonate solution and saturated sodium chloride solution
  2. dry with materialAfter drying over magnesium sulfate
  3. customthe ethyl acetate is removed by distillation under reduced pressure
  4. distillationthe benzyl alcohol is distilled off under a high vacuum
  5. customBy column chromatography on 150 g of silica gel in a system of dichloromethane/ethanol=10:1 and recrystallization from ethanol/hexane

Sources & evidence

ORD record
ord-86e3265b71a84c40be0687bfedf72b72
Source dataset
uspto-grants-1988_03
Patent number
US04731367

Reaction notes

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