Acetic Acid → (+/-) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate

HRID 921686Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 921686
[OH:1][CH2:2][CH:3]1[NH:8][CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1.[O:16]1[CH2:19][C:18](=O)[CH2:17]1.CC(O)=O.C([BH3-])#N.[Na+]>C(Cl)Cl.CO>[OH:1][CH2:2][CH:3]1[N:8]([CH:18]2[CH2:19][O:16][CH2:17]2)[CH2:7][CH2:6][N:5]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:4]1

Komponenten

7

Edukt 4

HCID 176Acetic AcidHCID 5003444Sodium cyanoborohydrideHCID 150242543-OxetanoneHCID 223865084-N-Boc-2-hydroxymethylpiperazine

Produkt 1

HCID 86708556(+/-) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylateAusbeute 62,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 887MethanolLösungsmittelHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

(+/−) Tert-butyl 3-(hydroxymethyl)piperazine-1-carboxylate (3.07 g, 14.19 mmol), oxetan-3-one (1.820 mL, 28.4 mmol), AcOH (1.625 mL, 28.4 mmol), and 4 Å molecular sieves were taken up in DCM (16 mL) and MeOH (16.00 mL), and the reaction was stirred at room temperature overnight. Sodium cyanoborohydride (4.46 g, 71.0 mmol) was added and the reaction was stirred at room temperature for 2 h. The reaction mixture was filtered through celite, rinsing with MeOH. The solvent was removed in vacuo and the material was quenched with 2M K3PO4 solution, and then extracted 2× with EtOAc. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The material was purified by flash column chromatography (0-8% MeOH/DCM). (+/−) Tert-butyl 3-(hydroxymethyl)-4-(oxetan-3-yl)piperazine-1-carboxylate (2.40 g) was obtained as a colorless oil.

Aufarbeitung

  1. filtrationThe reaction mixture was filtered through celite
  2. washrinsing with MeOH
  3. customThe solvent was removed in vacuo
  4. customthe material was quenched with 2M K3PO4 solution
  5. extractionextracted 2× with EtOAc
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe material was purified by flash column chromatography (0-8% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-3af88a335e03447396d0593d75988f7a
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09273057B2

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