Hydrochloric Acid → 2-Methylpentane

Participants

Reaction Steps

1-(Cyclopropylmethyl)-1,2,3,4-tetrahydro-3-methyl-2,4-dioxo-thieno[2,3-d]pyrimidine-5-carboxylic acid (6.8 g) was suspended in tetrahydrofuran (100 ml) and cooled to −78° C. to which lithium diisopropylamide (63 ml, 1M) was added. After complete addition the solution was left for 30 min before 2-(trifluoromethyl)-benzaldehyde, (7.4 mls) was added neat. After 1 h HCl(2M in water) was added and the reaction allowed to warm to room temperature. The reaction was concentrated in vacuo and partitioned between ethyl acetate and HCl (2M in water). The organic phase was collected, dried over magnesium sulfate, filtered and concentrated in vacuo and redissolved in diethyl ether, then washed with half saturated sodium hydrogen bicarbonate. The aqueous phase was collected and the diethyl ethyl was washed a seconded time with half saturated sodium hydrogen bicarbonate. The aqueous extracts were combined, acidified with HCl (conc.) and extracted with ethyl acetate. The organic phase was collected, dried over magnesium sulfate, filtered and concentrated in vacuo to brown gum. The gum was redissolved in trifluoroacetic acid (10 mls) and triethyl silane(5 mls) and stirred at room temperature for 72 hrs. The reaction was then concentrated in vacuo, and partioned between dichloromethane and water. The organics were collected, dried over magnesium sulfate, filtered and concentrated in vacuo before being purified by chromatography eluting with 20:1 dichloromethane:acetic acid and recrstallisation from ethyl acetate and isohexane, to yield 3.63 g of the subtitle compound.

Provenance & Evidence