Ammonia → 1,1-Diethyl-3-(6-methyl-2-hydroxymethyl-8alpha-ergolinyl)urea

HRID 569332Notes

Reaction equation

HRID 569332 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:9]([CH2:32][CH3:33])[C:10]([NH:12][C@H:13]1[CH2:27][C@H:26]2[C@@H:16]([CH2:17][C:18]3[C:28]4[C:21](=[CH:22][CH:23]=[CH:24][C:25]2=4)[NH:20][C:19]=3[CH:29]=[O:30])[N:15]([CH3:31])[CH2:14]1)=[O:11])[CH3:8].Cl.C(O)(=O)C(C(C(O)=O)O)O.N>C(OCC)(=O)C.O1CCCC1>[CH2:32]([N:9]([CH2:7][CH3:8])[C:10]([NH:12][C@H:13]1[CH2:27][C@H:26]2[C@@H:16]([CH2:17][C:18]3[C:28]4[C:21](=[CH:22][CH:23]=[CH:24][C:25]2=4)[NH:20][C:19]=3[CH2:29][OH:30])[N:15]([CH3:31])[CH2:14]1)=[O:11])[CH3:33]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 8752,3-Dihydroxybutanedioic AcidHCID 157465221,1-Diethyl-3-(6-methyl-2-formyl-8alpha-ergolinyl)ureaHCID 21226445Aluminium lithium hydride

Product 1

HCID 150861521,1-Diethyl-3-(6-methyl-2-hydroxymethyl-8alpha-ergolinyl)ureaYield 65%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Under argon, 320 mg (8 mmol) of lithium aluminum hydride is suspended in 20 ml of absolute, freshly distilled tetrahydrofuran. At room temperature, a solution of 1.40 g (4 mmol) of 1,1-diethyl-3-(6-methyl-2-formyl-8α-ergolinyl)urea in 40 ml of freshly distilled, absolute tetrahydrofuran is added dropwise. Then the mixture is stirred for 11/4 hours at room temperature. The batch is then cooled in an ice bath and combined with 20 ml of 1N hydrochloric acid. To this mixture is added 20 ml of 2N tartaric acid and the batch is layered over the ethyl acetate. For neutralization, 80 ml of 1N ammonia solution is added dropwise. The ethyl acetate phase is separated, and the aqueous phase is reextracted with ethyl acetate. The combined ethyl acetate phases are dried over sodium sulfate. The concentrated crude product is chromatographed on silica gel with methylene chloride/methanol 95:5 under pressure. The crude product (1.09 g) is crystallized from ethyl acetate, thus obtaining 0.94 g of 1,1-diethyl-3-(6-methyl-2-hydroxymethyl-8α-ergolinyl)urea (65% yield).

Workup

  1. temperatureThe batch is then cooled in an ice bath
  2. customThe ethyl acetate phase is separated
  3. dry with materialThe combined ethyl acetate phases are dried over sodium sulfate
  4. concentrationThe concentrated crude product
  5. customis chromatographed on silica gel with methylene chloride/methanol 95:5 under pressure
  6. customThe crude product (1.09 g) is crystallized from ethyl acetate

Sources & evidence

ORD record
ord-5709418a46524177981ce1f9778ee4cb
Source dataset
uspto-grants-1988_03
Patent number
US04731367

Reaction notes

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