Hydrochloric Acid → (R)-6-cyano-N-(1,1-dimethylethyl)-5-hydroxy-3-oxo-N-(phenylmethyl)hexanamide

HRID 129949ノート

反応式

HRID 129949 の反応式
[C:1]1([CH2:7][NH:8][C:9](=[O:11])[CH3:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-][CH:16]([CH3:18])[CH3:17])(C)C.[Li+].[C:20]([CH2:22][C@@H:23]([OH:30])[CH2:24][C:25](OCC)=[O:26])#[N:21].Cl.O1CCC[CH2:33]1>O1CCCC1.CCCCCCC>[C:20]([CH2:22][C@@H:23]([OH:30])[CH2:24][C:25](=[O:26])[CH2:10][C:9]([N:8]([C:16]([CH3:17])([CH3:18])[CH3:33])[CH2:7][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)=[O:11])#[N:21]

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2 回HCID 11500N-BenzylacetamideHCID 2724682Lithium diisopropylamideHCID 2733879Ethyl (3R)-4-cyano-3-hydroxybutanoate

生成物 1

HCID 53869197(R)-6-cyano-N-(1,1-dimethylethyl)-5-hydroxy-3-oxo-N-(phenylmethyl)hexanamide

試薬・触媒・溶媒 1

HCID 21263495Tetrahydrofuran heptane溶媒

実験手順

To a stirred -10° C. solution of N-1,1-dimethylethyl, N-phenylmethylacetamide (prepared from N-1,1-dimethylethyl, N-phenylmethyl amine, and acetyl chloride by refluxing for 2 hours in toluene) (102.5 g, 0.5 mol) in tetrahydrofuran (0.5 L) is slowly added a solution of lithium diisopropylamide in tetra-hydrofuran-heptane (0.25 L of 2M) while maintaining the temperature between -40° C. to -50° C., and the mixture is stirred at -20° C. to -30° C. for 30 minutes. (R)-4-cyano-3-hydroxybutyric acid, ethyl ester (Brower, supra) (20 g, 0.125 mol) as a solution in 200 mL or tetrahydrofuran is then added to the previous mixture. The reaction mixture is stirred for 30 minutes at -25° C. to -20° C., and transferred to a 2.2N aqueous hydrochloric acid solution (0.5 L). The aqueous layer is extracted with 300 mL of ethyl acetate, the aqueous layer is separated and reextracted with 100 mL of ethyl acetate, the extracts are combined and concentrated in vacuo to afford crude (R)-6-cyano-N-(1,1-dimethylethyl)-5-hydroxy-3-oxo-N-(phenylmethyl)hexanamide as an oil.

後処理

  1. temperaturewhile maintaining the temperature between -40° C. to -50° C.
  2. stirringThe reaction mixture is stirred for 30 minutes at -25° C. to -20° C.
  3. extractionThe aqueous layer is extracted with 300 mL of ethyl acetate
  4. customthe aqueous layer is separated
  5. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-0fb522bbf68640a8bd73329c87300f27
出典データセット
uspto-grants-1995_11
特許番号
US05470981

反応ノート

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