3-(2-fluoroethoxy)azetidine;hydrochloride

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Sodium triacetoxyborohydride (0.10 g) was added to a solution in NMP (1.5 mL) of (2S)-2-[{4-[(4-formylphenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (0.15 g) as obtained in Example 16-(1) and 3-(2-fluoroethoxy)azetidine hydrochloride (63 mg) as obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere. The mixture was stirred for 40 minutes at room temperature. Water and ethyl acetate were added, and the mixture was adjusted to pH 7.5 with a saturated aqueous solution of sodium hydrogen carbonate, whereafter the organic layer was isolated. The extract was washed with brine, and dried over anhydrous sodium sulfate. Then, the desiccant was filtered out, and the solvent was distilled off under reduced pressure. The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=80/20→50/50) to obtain (2S)-2-[{4-[(4-{[3-(2-fluoroethoxy)azetidin-1-yl]methyl}phenyl)ethynyl]benzoyl}(methyl)amino]-N,2-dimethyl-N′-(tetrahydro-2H-pyran-2-yloxy)propanediamide (yellow oil) (0.14 g, 81%). as obtained in Example 16-1-(2), under ice cooling in a nitrogen atmosphere was isolated The extract was washed with brine dried over anhydrous sodium sulfate Then, the desiccant was filtered out the solvent was distilled off under reduced pressure The resulting residue was purified by OH type silica gel column chromatography (gradient elution with chloroform/acetone=80/20→50/50)