4-Methylmorpholine → Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate

HRID 49852

Reaktionsgleichung

Reaktionsgleichung von HRID 49852
[C:1]([N:8]1[CH2:16][CH2:15][CH:11]([C:12](O)=[O:13])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+]>O1CCCC1>[C:1]([N:8]1[CH2:16][CH2:15][CH:11]([CH2:12][OH:13])[CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 4311764Sodium borohydride

Produkt 1

HCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateAusbeute 92,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

To a solution of Boc-isonipecotic acid (40 g, 0.17 mol) and N-methylmorpholine (19 mL, 0.17 mol) in tetrahydrofuran (900 mL) stirring at −10° C., ethyl chloroformate was slowly added (17 mL, 0.17 mol) via addition funnel. After 30 min, sodium borohydride was added (19.8 g, 0.5 mol) in one portion. The reaction mixture was stirred at −10° C. for 1 h; then it was slowly quenched with methanol. The solvent was removed in vacuo; the resulting residue was diluted with 10% aqueous acetic acid and partitioned between ethyl acetate and water. The aqueous layer was separated and extracted with additional ethyl acetate (2×500 mL). The combined organic extracts were dried with magnesium sulfate, filtered, and concentrated in vacuo to a solid residue which was chromatographed on silica gel. Elution with ethyl acetate-hexanes (1:9 to 1:1) provided the title compound (33.8 g, 90%) as a white solid.

Aufarbeitung

  1. additionvia addition funnel
  2. customthen it was slowly quenched with methanol
  3. customThe solvent was removed in vacuo
  4. additionthe resulting residue was diluted with 10% aqueous acetic acid
  5. custompartitioned between ethyl acetate and water
  6. customThe aqueous layer was separated
  7. extractionextracted with additional ethyl acetate (2×500 mL)
  8. dry with materialThe combined organic extracts were dried with magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a solid residue which
  11. customwas chromatographed on silica gel
  12. washElution with ethyl acetate-hexanes (1:9 to 1:1)

Quellen und Nachweise

ORD-Eintrag
ord-e45ee508e37449ea9b6fa0568defe10d
Quelldatensatz
uspto-grants-2004_03
Patentnummer
US06710057B2

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