Trifluoroacetic acid → 5,6-Dichloro-3-(2-(S)-azetidinylmethoxy)pyridine
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][N:12]2C(OC(C)(C)C)=O)[CH:5]=[N:6][C:7]=1[Cl:8].C(O)(C(F)(F)F)=O>C(Cl)Cl>[Cl:1][C:2]1[CH:3]=[C:4]([O:9][CH2:10][C@@H:11]2[CH2:14][CH2:13][NH:12]2)[CH:5]=[N:6][C:7]=1[Cl:8]Participants
4
Procedure
The compound of step 109b was dissolved in CH2Cl2 (10 mL) and TFA (10 mL) was added at 0° C. After 30 minutes of stirring the reaction was warmed to room temperature and stirred for an additional 45 minutes. Solvent was removed, and the residue was partitioned between sat'd K2CO3 solution and CH2Cl2. The aqueous layer was further extracted with CH2Cl2 (4×), and the combined organic extracts were dried over MgSO4 and concentrated. The crude material was chromatographed eltuing with 10% methanol/CHCl3 followed by 10% methanol/CHCl3 /0.5% NH4OH to give 475 mgs of a pale solid, 64% yield. m.p.=59-60° C. MS (CI) m/e 233 (M+H)+. 1H NMR (CDCl3, 300 MHz) δ: 8.01 (d, J=2.8 Hz, 1H), 7.37 (d, J=2.8 Hz, 1H), 4.33-4.24 (m, 1H), 4.08-3.98 (m, 2H), 3.73 (dd, J=15.8, 8.4 Hz, 1H), 3.49-3.41 (m, 1H), 2.44-2.21 (m, 2H).