Methanol → (2S)-1-(1,2-Dioxo-3,3-dimethylpentyl)2-(1-[3-(3-pyridyl)-1-propyl]-1H-tetrazol-5-yl)azetidine

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Reaction Conditions

Reaction Steps

(2S)-1-(1,2-Dioxo-2-methoxyethyl)-2-(1-[3-(3-pyridyl)-1-propyl]-1H-tetrazol-5-yl)azetidine from Reference Example 19 (95.8 mg, 0.290 mmol, 1.0 eq) was dissolved in dry tetrahydrofuran (THF) (1.0 mL) and cooled to about −78° C. under an argon atmosphere. To this solution, 1,1-dimethylpropylmagnesium chloride in THF (380 μL of 1M, 0.380 mmol, 1.3 eq) was introduced via syringe. After stirring the resulting homogeneous mixture at about −78° C. for about 3 hours, the mixture was poured into saturated ammonium chloride and extracted into ethyl acetate. The organic phase was washed with water, dried over sodium sulfate and concentrated. Flash chromatography of the residue (0-10% methanol in dichloromethane) afforded 8.7 mg (8% yield) of the product as a colorless semisolid along with 30.3 mg recovered starting material (32% yield). 1H NMR (CDCl3) δ 0.78 (t, 3H, J=6.9); 0.97-1.18 (series of s, 6H); 1.54 and 3.17 (series of m, 8H); 3.82-4.66 (series of m, 4H); 5.33-5.90 (series of dd, 1H); 7.21-7.31 (m, 1H); 7.57 (d, 1H, J=7.7); 8.49 (s, 2H).

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