[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@@H:9]1[CH2:12][OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N([CH2:19][CH3:20])CC)C.[C:21]1(C)[CH:26]=C[C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1.[OH-].[Na+]>ClCCl>[C:1]([O:5][C:6]([N:8]1[CH2:11][CH2:10][C@@H:9]1[CH2:12][O:13][S:27]([C:24]1[C:19]([CH3:20])=[CH:26][CH:21]=[CH:22][CH:23]=1)(=[O:29])=[O:28])=[O:7])([CH3:4])([CH3:3])[CH3:2]A solution of (R)-1-t-butyloxycarbonyl-2-azetidinemethanol (36.5 g, 0.195 mol) in 195 mL of dichloromethane was treated with triethylamine (35.6 ml, 0.255 mol) and then p-toluenesulfonyl chloride (48.5 g, 0.254 mol). The resulting mixture was stirred at room temperature for 16 hours. A 10% solution of sodium hydroxide was added rapidly and the mixture stirred for one hour. After phase separation, the aqueous phase was extracted with additional dichloromethane, combined with the organic phase, washed with NaHCO3 solution and brine, then dried (MgSO4), filtered, and concentrated in vacuo to give 63.1 g of (R)-1-t-butyloxycarbonyl-2-toluensulfonyloxymethylazetidine (94.8%). Next, a solution of 2-chloro-5-hydroxypyridine (from Step 1g below, 24 g, 0.185 mol) in DMF (690 mL) was treated with ground KOH (17.95 g, 0.295 mol) and stirred for 30 minutes at 80° C. To this mixture was rapidly added (2R)-1-t-butyloxycarbonyl)-2-toluensulfonyloxymethylazetidine (63.1 g) dissolved in DMF (395 mL) and the mixture was stirred for 16 hours at 80° C. The mixture was concentrated in vacuo to remove the DMF and the resultant residue was diluted with water and extracted with EtOAc (3×). The organic extracts were combined, dried (MgSO4), filtered and concentrated in vacuo to give 58.5 g of unpurified product. This material was chromatographed (silica gel, 25% EtOAc in hexane) to give 43.2 g of 5-(1-t-butyloxycarbonyl-(2R)-azetidinylmethyloxy)-2-chloropyridine as a clear oil (74%). A solution of 5-(1-t-butyloxycarbonyl-(2R)-azetidinylmethoxy)-2-chloropyridine (30 g, 0.1 mol) in 450 mL of dichloromethane at 0° C. was treated with 225 mL of trifluoroacetic acid dropwise over a 30 minute period. After two hours, the bulk of the solvent was removed in vacuo and the residue was diluted with ethyl acetate, washed with 1.0 M K2CO3 and brine, dried (Na2SO4) and concentrated in vacuo to give 19.1 g of a yellow oil. Flash silica gel chromatography (90:10 CHCl3:MeOH then 90:10:0.5 CHCl3:MeOH:NH4OH) gave 16.5 g of the title compound (83% yield): MS (CI/NH3) m/z: 199 (M+H)+; 1H NMR (CDCl3, 300 MHz) 67 2.21-2.43 (m, 2H), 3.42-3.50 (m, 1H), 3.69-3.78 (m, 1H), 3.98-4.07 (m, 2H), 4.25-4.34 (m, 1H), 7.22 (d, J=1.7 Hz, 2H), 8.07 (dd, 1.7, 2.0 Hz, 1H).
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