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

HRID 129949노트

반응식

HRID 129949 반응식
[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]

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 8028Tetrahydrofuran2회HCID 11500N-BenzylacetamideHCID 2724682Lithium diisopropylamideHCID 2733879Ethyl (3R)-4-cyano-3-hydroxybutanoate

생성물 1

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

시약·촉매·용매 1

HCID 21263495Tetrahydrofuran heptane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-0fb522bbf68640a8bd73329c87300f27
출처 데이터셋
uspto-grants-1995_11
특허 번호
US05470981

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