Process for the preparation of a PDE4 inhibitor

A process for the preparation of a compound of formula (IX):

• wherein n is 0 or 1, and R1 and R2 are independently H, linear or branched (C1-C6) alkyl, optionally substituted by one or more substituents selected from one or more halogen atoms, (C3-C7) cycloalkyl, (C5-C7)cycloalkenyl, (C5-C7) cycloalkenyl, linear or branched (C2-C6) alkenyl, aryl(C2-C6)alkenyl and linear or branched (C2-C6) alkynyl,
• which process comprises:
• (a) reacting a compound of formula (X):
• wherein n is 0 or 1, with a compound of formula (III):
• wherein X is —NHSO2Me or —NO2 and Z is —OH, chlorine, bromine, linear or branched (C1-C6)alkoxy, aryloxy, arylalkoxy, (C1-C6)alkylcarbonyloxy, arylcarbonyloxy or aryl(C1-C6)alkylcarbonyloxy to obtain a compound of formula (XI) wherein n is 0 or 1 or a compound of formula (XII):
• wherein R1, R2, and n have the above reported meanings;
• and
• when a compound of formula (XII) is obtained in step (a):
• (b) reducing said compound of formula (XII) to a compound of formula (XIII):
• wherein R1, R2, and n have the above reported meanings, and reacting said compound of formula (XIII) with methanesulfonyl halide to obtain said compound of formula (XI) wherein n has the above reported meanings;
• and wherein said compound of formula (X) in step (a) is obtained according to any one of the alternative steps (c1) or (c2):
• (c1) oxidizing a compound of formula (XIV):
• wherein n is 0 or 1 to obtain a compound of formula (XV):
• wherein n is 0 or 1, and subsequently enantioselectively reducing said compound of formula (XV) to obtain said compound of formula (X) wherein n has the above reported meanings;
• or
• (c2) chromatographically separating said compound of formula (XIV) wherein n is 0 or 1, to obtain said compound of formula (X) and a compound of formula (XVI)
• wherein n has the above reported meanings;
• and optionally oxidizing said compound of formula (XVI) to obtain said compound of formula (XV) and optionally subsequently reducing said compound of formula (XV) to said compound of formula (XIV) wherein n is 0 or 1 and which may be optionally chromatographically separated;
• and wherein all of said compounds of formula (XI), (X), (XII), (XIII), (XIV), (XV), or (XVI) wherein n is 1 can be obtained by oxidizing the corresponding compounds wherein n is 0.