Acetic Acid → 1-(6-Bromo-2-pyridinyl)-1-pentanol

Participants

Reaction Conditions

Reaction Steps

To a solution of nBuLi (26.40 mL of a 1.6M solution in hexanes, 42.24 mmol) in THF (25 mL) at −78° C. (dry-ice/acetone bath) was added a solution 2,6-dibromopyridine (10.00 g, 42.21 mmol) in THF (60 mL) drop-wise over 45 minutes under nitrogen. The resulting dark green coloured solution was stirred at −78° C. for 15 minutes and then valeraldehyde (6.70 mL, 63.01 mmol) was added drop-wise over 1 minute. The resulting dark purple coloured solution was stirred at −78° C. for 15 minutes and was then treated in one portion with a mixture of methanol (42 mL) and AcOH (2.70 mL, 47.16 mmol). The resulting pale yellow coloured solution was then allowed to warm to rt slowly over 1 hour. The mixture was then diluted with saturated aqueous NH4Cl (200 mL) and the product extracted with EtOAc (2×200 mL). The combined organic layer was then washed with brine (250 mL), dried (MgSO4), filtered and reduced to an orange oil (10.31 g, 100%). Purification of 7.14 g of this material by Biotage™ chromatography (silica) eluting with cyclohexane:EtOAc (gradient 100:1 to 1:1) afforded the title compound as a clear, pale yellow oil (4.48 g).

Provenance & Evidence