Process for the preparation of 2-isopentyl-2-isopropyl-1,3-dimethoxypropane

#This application is a National Stage application of PCT/EP2020/078730, filed Oct. 13, 2020, which is incorporated by reference in its entirety herein.

#Several methods have been reported in literature for the preparation of diethers compounds, especially 2,2-disubstituted-1,3-dimethoxy propane, such as 2-isopentyl-2-isopropyl-1,3-dimethoxypropane.

#EP 0 361 493 A1 discloses the alkylation of diethyl malonate using ethyl malonate, alkyl bromide and lithium aluminium hydride which are costly and not necessarily environmentally benign.

#The present invention relates to a process for the preparation of 2-isopentyl-2-isopropyl-1,3-dimethoxypropane (Formula 1), said process comprising the steps of: i) contacting iso-valeraldehyde (Formula A) with an aqueous solution of a hydroxide base selected from the group consisting of sodium hydroxide (NaOH), potassium hydroxide (KOH) or a combination thereof, said solution having an amount of said hydroxide base of at least 15% w/v, and methanol (or ethanol); to form (2Z)-2-isopropyl-5-methyl-2-hexenal (Formula B); ii) contacting (2Z)-2-isopropyl-5-methyl2-hexenal (Formula B) with a reducing catalyst system to form 2-isopropyl-5-methylhexanal (Formula C); iii) contacting 2-isopropyl-5-methylhexanal (Formula C) with formaldehyde and an inorganic base to form 2-isopentyl-2-isopropylpropane-1,3-diol (Formula D); and iv) contacting 2-isopentyl-2-isopropylpropane-1,3-diol (Formula D) with a methylation agent and a base to form 2-isopentyl-2-isopropyl-1,3-dimethoxypropane (Formula 1).

#In an embodiment, step i) comprises: contacting iso-valeraldehyde (Formula A) with methanol and gradually adding the aqueous solution of a hydroxide base, preferably over a period of between 20 and 50 minutes, while the temperature is maintained below 45° C.; after completion of the addition of the hydroxide heating the reaction mixture to a temperature of between 45 and 60° C. and maintained at that temperature for a period of between 10 and 50 minutes; separating an aqueous hydroxide phase from an organic product phase; optionally washing the organic product phase with water to obtain the product as an oil.

#In an embodiment, step ii) comprises: contacting (2Z)-2-isopropyl-5-methyl-2-hexenal (Formula B) with an aqueous solution of hydroxide; adding Ni/Al alloy in at least three portions, each portion being added gradually over a period of between 30 and 60 minutes and stirring the reaction mixture in between the addition of each portion for a period of between 30 and 60 minutes; while maintaining the temperature between 15 and 25° C. removing the alloy by filtration; optionally washing the rententate with water; separating an aqueous hydroxide phase of the filtrate from an organic product phase; optionally extracting the aqueous hydroxide phase with an organic extractant which extract is combined with the organic product phase; evaporating the organic product phase to obtain the product according to Formula C.