Hexane → (R)-tert-butyl 3-(3-chloro-2-fluorobenzoyl)piperidine-1-carboxylate

HRID 253531

Reaktionsgleichung

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[F:8].[Li]CCCC.CCCCCC.CON(C)[C:23]([C@@H:25]1[CH2:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1)=[O:24]>C1COCC1>[Cl:1][C:2]1[C:3]([F:8])=[C:4]([CH:5]=[CH:6][CH:7]=1)[C:23]([C@@H:25]1[CH2:30][CH2:29][CH2:28][N:27]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:26]1)=[O:24]

Komponenten

Reaktionsbedingungen

Temperatur: -75 °C

Versuchsvorschrift

To a stirred solution of 1-chloro-2-fluoro-benzene (13.0 g, 0.1 mol) in THF (250 mL) at −75° C. was added dropwise 2.5 M BuLi in hexane (40 mL, 0.1 mol) over 45 min. After additional stirring for 30 min at −75° C., a solution of (R)-tert-butyl 3-(methoxy(methyl)carbamoyl)-piperidine-1-carboxylate (21.76 g, 0.08 mol) in THF (100 mL) was added dropwise over 30 min. The mixture was allowed to warm from −70° C. to 0° C. The mixture was quenched with satd aq NH4Cl, extracted with EtOAc (3×) and the combined organic layers were dried over Na2SO4. Solvent removal and flash column chromatography, eluting with 5% EtOAc/PE afforded (R)-tert-butyl 3-(3-chloro-2-fluorobenzoyl)piperidine-1-carboxylate (19.2 g, 70%). 1H NMR (400 MHz, CDCl3): 1.45 (s, 9H), 1.63 (m, 2H), 1.76 (m, 1H), 2.06 (m, 1H), 2.87 (m, 1H), 3.15 (m, 1H), 3.25 (m, 1H), 3.9 (m, 1H), 4.2 (m, 1H), 7.18 (m, 1H), 7.60 (m, 2H). MS (E/Z): 342 (M+H+).

Aufarbeitung

temperatureto warm from −70° C. to 0° C
customThe mixture was quenched with satd aq NH4Cl
extractionextracted with EtOAc (3×)
dry with materialthe combined organic layers were dried over Na2SO4
customSolvent removal and flash column chromatography
washeluting with 5% EtOAc/PE

Quellen und Nachweise

ORD-Eintrag: ord-2081c657440a426ebf725840f6df1689
Quelldatensatz: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patentnummer: US07872028B2

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