Reaktion #453024

Reaktionsgleichung

5-phenyl-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine

TFA

→

title compound

5-Phenyl-6-chloro-3-(2-(S)-azetidinylmethoxy)pyridine hydrochloride

Lösungsmittel

CH2Cl2

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe volatiles were then removed under vacuum
2. 2
   Extraktionextracted with CH2Cl2, which
3. 3
   Trocknenwas dried over MgSO4
4. 4
   Einengenconcentrated
5. 5
   SonstigeThe residue was chromatographed on a silica gel column
6. 6
   Wascheneluting with CH2Cl2 :MeOH:NH4OH 10:1:0.1
7. 7
   Sonstigeto afford

Vorschrift

To 5-phenyl-6-chloro-3-(1-BOC-2-(S)-azetidinylmethoxy)pyridine from step 67a (380 mg) was added TFA in CH2Cl2 at 0° C., and the mixture was stirred for 30 minutes. The volatiles were then removed under vacuum. The residue was neutralized with NaHCO3 to pH 8, then extracted with CH2Cl2, which was dried over MgSO4 and concentrated. The residue was chromatographed on a silica gel column, eluting with CH2Cl2 :MeOH:NH4OH 10:1:0.1 to afford to give the free base of the title compound. MS (CI/NH3) m/z 275 (M+H)+, 277 (M+2H)+. 1H NMR (CDCl3, 300 MHz) δ2.21-2.46 (m, 2H), 3.41-3.50 (m, 1H), 3.73 (dd, J=7.5, 8.0 Hz, 1H), 4.0-4.12 (m, 2H), 4.25-4.35 (m, 1H), 7.26 (d, J=3 Hz, 1H), 7.41-7.48 (m, 5H), 8.09 (d, J=3 Hz, 1H). The base was converted to the salt by treatment with hydrogen chloride saturated EtOH to give the title compound (256 mg). mp 148-150° C. MS (CI/NH3) m/z 275 (M+H)+. 1H NMR (D2O, 300 MHz) δ2.66-274 (m, 2H), 4.06-4.21 (m, 3H), 4.46 (d, J=4.1, 2H), 4.92-5.01 (m, 1H), 7.50-7.59 (m, 5H), 7.60 (d, J=3.0, 1H), 8.20 (d, J=3.0, 1H). Anal. Calcd for C15H15N2OCl·2 HCl: C, 51.82; H, 4.93; N, 8.06. Found: C, 52.10; H, 5.29; N, 7.70. [α]25D=+7.5° (c 0.16, MeOH).

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