Ammonia → 3-(9,10-Didehydro-2-hydroxymethyl-6-methyl-8alpha-ergolinyl)-1,1-diethylurea

HRID 569335Notes

Reaction equation

HRID 569335 reaction equation
[CH:1]([C:3]1[NH:17][C:16]2[C:18]3[C:4]=1[CH2:5][C@@H:6]1[C:11]([C:12]=3[CH:13]=[CH:14][CH:15]=2)=[CH:10][C@H:9]([NH:19][C:20](=[O:26])[N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH2:8][N:7]1[CH3:27])=[O:2].[H-].[Al+3].[Li+].[H-].[H-].[H-].Cl.C(O)(=O)C(C(C(O)=O)O)O.N>C(OCC)(=O)C.O1CCCC1>[OH:2][CH2:1][C:3]1[NH:17][C:16]2[C:18]3[C:4]=1[CH2:5][C@@H:6]1[C:11]([C:12]=3[CH:13]=[CH:14][CH:15]=2)=[CH:10][C@H:9]([NH:19][C:20](=[O:26])[N:21]([CH2:24][CH3:25])[CH2:22][CH3:23])[CH2:8][N:7]1[CH3:27]

Participants

8

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 8752,3-Dihydroxybutanedioic AcidHCID 21226445Aluminium lithium hydrideHCID 867420563-(9,10-Didehydro-2-formyl-6-methyl-8alpha-ergolinyl)-1,1-diethylurea

Product 1

HCID 867420573-(9,10-Didehydro-2-hydroxymethyl-6-methyl-8alpha-ergolinyl)-1,1-diethylureaYield 65.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Under argon, a solution of 244 mg (0.67 mmol) of 3-(9,10-didehydro-2-formyl-6-methyl-8α-ergolinyl)-1,1-diethylurea in 25 ml of absolute, freshly distilled tetrahydrofuran is added dropwise to a suspension of 52 mg (1.45 mmol) of lithium aluminum hydride in 3 ml of absolute, freshly distilled tetrahydrofuran at room temperature. The mixture is stirred for one hour at room temperature. The batch is cooled in an ice bath and combined in succession with 3 ml of 1N hydrochloric acid and 3 ml of 2N tartaric acid. The mixture is layered over with ethyl acetate and made alkaline with 12 ml of 1N ammonia solution. The ethyl acetate phase is separated and the aqueous phase is additionally extracted twice with ethyl acetate. The combined ethyl acetate phases are dried over sodium sulfate and concentrated. The product is crystallized from ethyl acetate, yielding 161 mg of 3-(9,10-didehydro-2-hydroxymethyl-6-methyl-8α-ergolinyl)-1,1-diethylurea (65% yield).

Workup

  1. temperatureThe batch is cooled in an ice bath
  2. customThe ethyl acetate phase is separated
  3. extractionthe aqueous phase is additionally extracted twice with ethyl acetate
  4. dry with materialThe combined ethyl acetate phases are dried over sodium sulfate
  5. concentrationconcentrated
  6. customThe product is crystallized from ethyl acetate

Sources & evidence

ORD record
ord-1a5dccd641584614bea1c97a00dedd14
Source dataset
uspto-grants-1988_03
Patent number
US04731367

Reaction notes

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