Hydrochloric Acid → (1S,5R)-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester

HRID 1917348ノート

反応式

HRID 1917348 の反応式
[C:1]([O:5][C:6]([C@@:8]1([CH2:22][CH2:23][C:24](OC)=[O:25])[CH2:12][C:11](=[O:13])[N:10]([C@@H:14]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH3:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N-]C(C)C)(C)C.[Li+].CCCCCCC.O1CCCC1.C(C1C=CC=CC=1)C.Cl>O1CCCC1>[C:1]([O:5][C:6]([C@@:8]12[CH2:22][CH2:23][C:24](=[O:25])[C@@H:12]1[C:11](=[O:13])[N:10]([C@@H:14]([C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH3:15])[CH2:9]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

参加物

5

反応物 3

HCID 313Hydrochloric AcidHCID 67490882HCID 67490882、化合物HCID 86590273LDA THF ethylbenzene heptane

生成物 1

HCID 67490920(1S,5R)-4,6-dioxo-3-[(1R)-1-phenylethyl]-3-azabicyclo[3.3.0]octan-1-ylcarboxylic acid tert-butyl ester収率 69.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

(3S)-3-(2-Methoxycarbonyl-1-ethyl)-5-oxo-1-[(1R)-1-phenylethyl]pyrrolidine-3-carboxylic acid tert-butyl ester (35.0 g, 93.2 mmol) was dissolved in tetrahydrofuran (1 L). A 2 M lithium diisopropylamide/heptane/tetrahydrofuran/ethylbenzene solution (100 mL, 200 mmol) was added dropwise in a nitrogen atmosphere at an internal temperature of −69° C. over 30 minutes. After stirring at the same temperature for one hour, the reaction solution was poured into a 1N hydrochloric acid solution (2 L) in an ice bath, followed by extraction with ethyl acetate (2 L, 1 L). The organic layers were combined, washed with brine, and dried over anhydrous sodium sulfate. After filtration, the filtrate was concentrated under reduced pressure, and the precipitated solid was collected by filtration to give 22.2 g of the title compound as pale red crystals. The filtrate was further concentrated to give 2.88 g of the title compound as pale red crystals. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (hexane:ethyl acetate=1:1) to give 2.09 g of the title compound as colorless crystals.

後処理

  1. extractionfollowed by extraction with ethyl acetate (2 L, 1 L)
  2. washwashed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. filtrationthe precipitated solid was collected by filtration

出典と根拠

ORDレコード
ord-893b8d1533a44660b56d01a79bd77412
出典データセット
uspto-grants-2013_12
特許番号
US08618094B2

反応ノート

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