Hydrochloric Acid → tert-Butyl (R)-6-Cyano-5-hydroxy-3-oxohexanoate

HRID 466293

Reaktionsgleichung

Reaktionsgleichung von HRID 466293
C([N-]C(C)C)(C)C.[Li+].[C:9]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])(=[O:11])[CH3:10].[C:17]([CH2:19][C@@H:20]([OH:27])[CH2:21][C:22](OCC)=[O:23])#[N:18].Cl>O1CCCC1>[C:17]([CH2:19][C@@H:20]([OH:27])[CH2:21][C:22](=[O:23])[CH2:10][C:9]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])#[N:18]

Komponenten

6

Edukt 4

HCID 313Hydrochloric AcidHCID 10908tert-Butyl acetateHCID 2724682Lithium diisopropylamideHCID 2733879Ethyl (3R)-4-cyano-3-hydroxybutanoate

Produkt 1

HCID 9794547tert-Butyl (R)-6-Cyano-5-hydroxy-3-oxohexanoate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a stirred -50° C. solution of lithium diisopropylamide (100 kg of 2 M) in tetrahydrofuranheptane is added tertiary-butyl acetate (30 kg, 255 mol) followed by a rinse of 3 kg of tetrahydrofuran and the mixture is stirred at -45° C. to -5° C. for 50 minutes. (R)-4-cyano-3-hydroxybutyric acid, ethyl ester (10 kg, 64 mol) as a solution in 30 kg of tetrahydrofuran is then added to the previous mixture. The reaction mixture is stirred for 30 minutes at -5° C. to -30° C., and transferred to 240 L of 0° C. 2.8 N aqueous hydrochloric acid solution. The aqueous layer is extracted with 50 kg of ethyl acetate, the aqueous layer is separated and reextracted with 36 kg of ethyl acetate, the extracts are combined and concentrated in vacuo to afford crude (5R)-1,1-dimethylethyl 6-cyano-5-hydroxy-3-oxo -hexanoate which is not isolated. A small sample is purified by column chromatography on flash silica gel eluting with 1:1 hexane:ethyl acetate. 1H--NMR: (CDCl3) 1.48 (9H, s), 2.61 (2H, m), 2.88 (2H, d), 3.43 (2H, s), 3.58 (1H, bs), 4.40 (1H, m). MS:(EI) m/e, (%): 229 (3), 228(26),173(10), 172(100), 154(62), 112(30), 59(50), 57(77).

Aufarbeitung

  1. washa rinse of 3 kg of tetrahydrofuran
  2. stirringThe reaction mixture is stirred for 30 minutes at -5° C. to -30° C.
  3. customtransferred to 240 L of 0° C
  4. extractionThe aqueous layer is extracted with 50 kg of ethyl acetate
  5. customthe aqueous layer is separated
  6. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-49b4e1434ff54fe3bdbd9e355ccf5f2d
Quelldatensatz
uspto-grants-1992_10
Patentnummer
US05155251

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