5-Bromo-2,4-bis(1,1-dimethylethoxy)pyrimidine → (+/-)-5-(9,10-Dihydro-4-hydroxy-2,7-dimethyl-4H-benzo[5,6]cyclohepta[1,2-d]oxazol-4-yl)-2,4(1H,3H)-pyrimidinedione

Participants

Reaction Steps

To a solution of the product from example 1 step (vi) (9 g) in dry tetrahydrafuran (100 ml) under nitrogen at −78° C. was added n-butyllithium (2.5M, 14.3 ml) dropwise over 1 min. After 30 min a warm solution of the product from step (v) (6.73 g) in tetrahydrofuran (350 ml) was added rapidly via cannula. After further stirring for 1 h the cooling bath was removed and the mixture allowed to stir at room temperature for 30 min. The reaction mixture was quenched with saturated brine and extracted with ethyl acetate (×2). The combined organic extracts were dried over magnesium sulphate and solvent removed under reduced pressure to leave a pale yellow foam. This was dissolved in acetic acid (100 ml) and stired at room temperature for 16 h. The solvent was evaporated under reduced pressure and the residue azeotroped with toluene (×2) to remove last traces of acetic acid. The remaining residue was triturated with diethyl ether/isohexane mixtures and filtered to give the subtitle product as a beige solid.

Provenance & Evidence