3-Bromopropionitrile → 1-Tert-butyl 4-ethyl 4-(2-cyanoethyl)piperidine-1,4-dicarboxylate

HRID 41536

Reaktionsgleichung

Reaktionsgleichung von HRID 41536
[C:1]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[Li+].CC([N-]C(C)C)C.Br[CH2:28][CH2:29][C:30]#[N:31]>C1COCC1>[C:30]([CH2:29][CH2:28][C:11]1([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:12][CH2:13][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:9][CH2:10]1)#[N:31]

Komponenten

5

Edukt 3

HCID 170203-BromopropionitrileHCID 2724682Lithium diisopropylamideHCID 27588121-Tert-butyl 4-ethyl piperidine-1,4-dicarboxylate

Produkt 1

HCID 672523241-Tert-butyl 4-ethyl 4-(2-cyanoethyl)piperidine-1,4-dicarboxylateAusbeute 41,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of ethyl N-Boc-piperidine-4-carboxylate (10.0 g, 38.86 mmol) in THF (200 mL) was added LDA (2 M solution in Hexane, 38.86 mL, 77.72 mmol) at −78° C. and stirred for 30 min. 3-bromo propionitrile (6.25 g, 46.63 mmol) was then added at −78° C. The resulting reaction mixture was stirred at −60° C. for 4 h and quenched with saturated NH4Cl solution. Ethyl acetate was added and the organic layer was extracted with water and brine. The organic layer was dried over Na2SO4, filtered and concentrated. The crude product was purified by column chromatography using 10% ethyl acetate in hexane to yield the title compound as a pale yellow liquid (5.0 g, 40%). [1H-NMR (DMSO-d6, 300 MHz): δ 4.15 (q, 2H), 3.78-3.54 (m, 2H), 2.93-2.72 (m, 2H), 2.43 (t, 2H), 2.02-1.78 (m, 4H), 1.45-1.29 (m, 11H), 1.22 (t, 3H); HPLC RtA=4.703 min (93%); LCMS RtA=1.881, [M+H-Boc]+=211.1].

Aufarbeitung

  1. customThe resulting reaction mixture
  2. stirringwas stirred at −60° C. for 4 h
  3. customquenched with saturated NH4Cl solution
  4. additionEthyl acetate was added
  5. extractionthe organic layer was extracted with water and brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography

Quellen und Nachweise

ORD-Eintrag
ord-b130606dece64225852ec4b295a7726a
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08530648B2

Verknüpfte Notizen

Wird geladen…