Continuous-flow catalytic dehydration process for the synthesis of macrocyclic compounds

A continuous flow process for preparation of macrocyclic compound of formula (I),

• wherein:
• A is CH2 or CO;
• A1 is O or NH;
• A2 is O or S;
• R is hydrogen, OH, C1-6alkyl, halogen, substituted or unsubstituted phenyl, or C1-6alkyloxy;
• or R along with hydrogen of phenyl ring form naphthyl ring, wherein the substitution is one or more group selected from halogen or OH;
• R1 is hydrogen, or C1-6alkyl;
• R2 is hydrogen, OH, C1-6alkyl, halogen, substituted or unsubstituted phenyl, or C1-6alkyloxy, or R2 along with hydrogen of phenyl ring form naphthyl ring, wherein the substitution is one or more group selected from halogen or OH;
• n is 0, 1, 2, 3, 4 or 5;
• m is 0, 1 or 2;
• and
• represents C2-14 linear alkyl;
• wherein the one or more CH2 of C2-14 linear alkyl is optionally replaced with O or S.
• wherein the process comprises the steps of:
• dissolving a compound of formula (Ia) (wherein X is CH2OH, COOH or CONH2;
• A2, R, R1, R2, n and m are as defined above) in a solvent to obtain a solution;
• and
• reacting the solution with a heterogeneous catalyst present in a continuous flow reactor at a temperature in a range of 100° C. to 150° C. with the flow rate in a range of 0.05 mL/min to 2 mL/min at back pressure in a range of 2.5 to 4 bar to obtain the compound of formula (I).