Sodium Bicarbonate → Letermovir

Participants

Reaction Steps

(2S,3S)-2,3-Bis[(4-methylbenzoyl)oxy]succinic acid-methyl {8-fluoro-2-[4-(3-methoxyphenyl)-piperazin-1-yl]-3-[2-methoxy-5-(trifluoromethyl)phenyl]-3,4-dihydroquinazolin-4-yl}acetate (1:1 salt) (25.1 g) are suspended in ethyl acetate (250 ml) and shaken with saturated aqueous sodium bicarbonate solution (250 ml) until both phases are clear. The phases are separated and the organic phase is concentrated in a rotary evaporator. The residue is dissolved in 1,4-dioxane (250 ml) and 1N sodium hydroxide solution (77.4 ml) and stirred at room temperature for 18 h. Subsequently, the pH is adjusted to 7.5 using 1N hydrochloric acid (ca. 50 ml), MIBK (240 ml) is added, then the pH is readjusted to 7.0 using 1N hydrochloric acid (ca. 15 ml). The phases are separated, and the organic phase is dried over sodium sulphate and concentrated. The residue is dissolved in ethanol (90 ml) and concentrated, then again dissolved in ethanol (90 ml) and concentrated. The solidified foam is dried at 45° C. for 18 h in the VDO using entraining nitrogen. A total of 12 g of (S)-{8-fluoro-2-[4-(3-methoxyphenyl)piperazin-1-yl]-3-(2-methoxy-5-trifluoromethylphenyl)-3,4-dihydro-quinazolin-4-yl}acetic acid are thus obtained as an amorphous solid, corresponding to 81.2% of theory.

Provenance & Evidence