Diisopropylamine → 4-But-3-enyl-tetrahydro-pyran-4-carboxylic acid methyl ester

Participants

Reaction Conditions

Reaction Steps

A round bottom flask (250 mL) was charged with 6.1 g (60 mmol) of diisopropylamine dissolved in THF (100 mL). This solution was cooled to −78° C. To this was added 24 mL of 2 M butyllithium in hexane and stirred for 15 min, warmed up to 0° C. for 20 min, re-cooled to −78° C. To this was added tetrahydro-pyran-4-carboxylic acid methyl ester (7.2 g, 50 mmol) in THF (10 mL). There was almost no color change. This was stirred at −78° C. for 45 min. Then, a mixture of 5 g of HMPA and bromo-butene (8.78 g, 65 mmol) was added via cannula at −78° C. There was no noticeable change. After addition of about half of the amounts of HMPA and bromo-butene, the ice-acetone bath was removed. When the addition was complete, the flask was submerged into an ice-water bath, stirred for 20 min; and then stirred at rt for 2 h. TLC (EtOAc/Heptane 1:1, paraldehyde visualization) showed the reaction was complete. The reaction mixture was poured into ice-water (100 mL) and ether (50 mL). The two layers were separated; the aqueous layer was extracted with ether (3×50 mL). The combined organic layers were washed with brine, dried (K2CO3), filtered, and concentrated in vacuo to obtain 10.4 g (87%) of the title product as a slightly yellow liquid. The material is pure enough to be used in the next step without further purification.

Provenance & Evidence