Citric Acid → HCID 86709847, compound

Participants

Reaction Conditions

Reaction Steps

In Step 3-2, the compound of Formula XIV is mixed with: (i) a solvent which is preferably 1,3-dimethyl-2-imidazolidinone (DMI) or tetrahydrofuran, (ii) methyl formate or ethyl formate; and (iii) optionally a Lewis acid, for example, CuCl or ZnCl2. When a Lewis acid is employed, typically the Lewis acid is added in amounts of up to about 1 eq. relative to the amount of the compound of Formula XIV employed. In some embodiments a Lewis acid is employed in this step to increase yield and simplify workup of the reaction mixture. Following the addition of the constituents, the reaction mixture is cooled to a temperature of from about [−100]° C. to about [−55]° C., then, maintaining the temperature of the reaction mixture, to the reaction mixture is added lithium bis(trimethylsilyl)amide (LiHMDS) followed by chlorotrimethylsilane (TMSCl). After addition is complete, the reaction mixture is warmed to a temperature of from about 0° C. to about [+10]° C. and combined with an aliquot of a citric acid or acetic acid solution. The resultant intermediate is treated with trifluoroacetic acid to obtain the pyrrolo[1,2-c]oxazole-7a-carbaldehyde of Formula XV.

Provenance & Evidence