1-Chloroethyl chloroformate → 3-(4-Fluorophenoxy)azetidine hydrochloride

HRID 341492

Reaktionsgleichung

Reaktionsgleichung von HRID 341492
C1(C(C2C=CC=CC=2)[N:8]2[CH2:11][CH:10]([O:12][C:13]3[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=3)[CH2:9]2)C=CC=CC=1.[Cl:26]C(OC(Cl)=O)C>ClCCCl>[ClH:26].[F:19][C:16]1[CH:17]=[CH:18][C:13]([O:12][CH:10]2[CH2:9][NH:8][CH2:11]2)=[CH:14][CH:15]=1

Komponenten

4

Edukt 2

HCID 5213051-Chloroethyl chloroformate2×HCID 150533691-Benzhydryl-3-(4-fluorophenoxy)azetidine2×

Produkt 1

HCID 214287323-(4-Fluorophenoxy)azetidine hydrochlorideAusbeute 91 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

To a stirred solution of 1-(diphenylmethyl)-3-(4-fluorophenoxy)azetidine (Intermediate 123, 3.2 g, 9.6 mmol) in DCE (20 ml) was added dropwise 1-chloroethylchloroformate (1.6 ml, 1.5 eq). The mixture was stirred 10 min then heated to reflux for 6 h. More 1-chloroethylchloroformate was added (1.6 ml) and heating was continued for 3 h. The mixture was cooled to room temperature and concentrated under vacuum. The residue was dissolved in MeOH (20 mL) and left to stand overnight. The mixture was heated under reflux and stirred for 1 h, then cooled to room temperature and concentrated under vacuum. The residue was crystallised under diethyl ether; the solid was broken up with a spatula, filtered off—washing with diethyl ether—and dried under vacuum to give the title compound as a cream solid (1.78 g, 91%). Method B HPLC-MS: MH+ requires m/z=168 Found: m/z=168, Rt=0.69 min (92%). 1H NMR (250 MHZ, DMSO-d6) δ ppm 9.50 (2H, br s), 7.15 (2H, t), 6.89 (2H, dd), 5.03 (1H, m), 4.39 (2H, m), and 3.93 (2H, m).

Aufarbeitung

  1. temperaturethen heated
  2. temperatureto reflux for 6 h
  3. temperatureheating
  4. waitwas continued for 3 h
  5. concentrationconcentrated under vacuum
  6. dissolutionThe residue was dissolved in MeOH (20 mL)
  7. waitleft
  8. waitto stand overnight
  9. temperatureThe mixture was heated
  10. temperatureunder reflux
  11. stirringstirred for 1 h
  12. temperaturecooled to room temperature
  13. concentrationconcentrated under vacuum
  14. customThe residue was crystallised under diethyl ether
  15. filtrationfiltered
  16. washoff—washing with diethyl ether—
  17. customdried under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-5ef3419f6659469bb0cbb0187e80d914
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08895733B2

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