1-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acid → 1-Tert-butyl 4-chloromethyl piperidine-1,4-dicarboxylate

HRID 1091342Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1091342
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=[O:15])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])(O)=O.[Na+].S(Cl)(O[CH2:26][Cl:27])(=O)=O>ClCCl.O.S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC>[N:8]1([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:13][CH2:12][CH:11]([C:14]([O:16][CH2:26][Cl:27])=[O:15])[CH2:10][CH2:9]1

Komponenten

7

Edukt 3

HCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 516892Sodium BicarbonateHCID 2733556Chloromethyl chlorosulfate

Produkt 1

HCID 101075661-Tert-butyl 4-chloromethyl piperidine-1,4-dicarboxylateAusbeute 96 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 94433Tetrabutylammonium hydrogen sulfateKatalysatorHCID 962WaterLösungsmittel2×HCID 6344DichloromethaneLösungsmittel3×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a mixture of 1-(tert-butoxycarbonyl)piperidine-4-carboxylic acid (3 g, 13.1 mmol) in dichloromethane (40 mL) and water (50 mL) was added NaHCO3 (4.4 g, 52.3 mmol) and tetrabutylammonium hydrogen sulfate (444 mg. 1.3 mmol). After stirring the mixture in an ice bath at 0° C. for ˜10 min, chloromethyl chlorosulfate (2.59 g, 15.7 mmol) in 10 mL of dichloromethane was added dropwise. The reaction mixture was allowed to warm up to rt and stirred vigorously overnight. The mixture was transferred to a separatory funnel with dichloromethane and water (200 mL, each). The organic layer was washed with additional water and brine, dried (Na2SO4), and concentrated in vacuo to give 1-tert-butyl 4-chloromethyl piperidine-1,4-dicarboxylate as a clear oil (3.5 g. 96% yield). This material was used without further purification. 1H NMR (DMSO-d6) δ 1.26-1.48 (m. 11H, CHH, CHH, tertBu), 1.83 (dd. J=3.0, 13.2 Hz, 21-1, CHH, CHH), 2.58-2.75 (m, 1H, CH), 2.74-2.99 (m, 2H, CHH, CHH), 3.61-4.02 (m, 2H, CHH, CHH), 5.87 (s, 2H, CH2O); 13C NMR (DMSO-d6) δ 27.16, 27.98, 39.58, 42.35, 69.41, 78.67, 153.75, 172.25; LCMS: MH=278.

Aufarbeitung

  1. temperatureto warm up to rt
  2. stirringstirred vigorously overnight
  3. washThe organic layer was washed with additional water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-b2775f1d43dc4617912fcc75abd183b7
Quelldatensatz
uspto-grants-2012_03
Patentnummer
US08129375B2

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