Process for preparing an intermediate of the macrocyclic protease inhibitor tmc 435

A process for preparing a compound of formula (II), wherein R1 is C1-6alkyl,

• comprising
• a) acylating a diene compound of formula (I), wherein R1 is C1-6alkyl,
• with a halogenated acyl compound (R2—CO)2O or R2—COCl, wherein R2 is polyhaloC1-4alkyl, followed by a ring-closing metathesis reaction of the acylated reaction product with a suitable catalyst in a reaction-inert solvent to yield a compound of formula (III);
• and
• b) removing the halogenated acyl group from compound (III) thus obtaining the compound of formula (II) wherein R1 is C1-6alkyl.

A compound of formula:

• wherein Rx represent —C(O)R2,
• n is 0-8;
• G represents —ORx1 or —N(H)SO2Rx2;
• Rx1 represents hydrogen or C1-6 alkyl;
• Rx2 represents C1-6 alkyl or C3-6 cycloalkyl;
• X represents N or CH;
• Y represents N or CH;
• when Y represents N, then Y1 represents hydrogen or C1-6 alkyl;
• when Y represents CH, then Y1 represents —C(O)—Rx3, —S(O)1-2—Rx3, —C(S)—Rx3, —N(Rx3)—Rx4, —N(H)—C(O)—O—Rx3 or —N(H)—C(O)—Rx4;
• Rx3 and Rx4 independently represent C1-6 alkyl, C3-6 cycloalkyl, aryl or heteroaryl (which latter two groups are optionally substituted by one or more substituents selected from halo and C1-6 alkyl);
• L represents —O— or —O—C(O)—;
• Ry represents aryl, heteroaryl or cyclic non-aromatic group, all of which are optionally substituted by one or more substituents.