Substituted heterocycle fused gamma-carbolines synthesis

A method for preparing a compound of Formula 1J,

• in free or salt form, wherein R is H, and Q is selected from 4-(4-fluorophenyl)-4-oxobutyl and 3-(4-fluorophenoxy)propyl;
• comprising the steps of (a) reacting a compound of Formula 1E′,
• in free or salt form, wherein
• (i) B is a protecting group;
• with (i) an alkyl haloacetate of the formula XCH2C(O)OR′ wherein X is a halide selected from Cl, Br and I, and R′ is C1-6 alkyl (e.g., ethyl), (ii) optionally a base, and (iii) optionally an alkali metal or ammonium iodide or bromide (e.g. potassium iodide or tetrabutylammonium bromide), to form an intermediate of Formula 1F,
• in free or salt form, wherein B is a protecting group and R is H;
• (b) deprotecting the piperidine nitrogen of the compound of Formula 1F to yield the compound of Formula 1I,
• in free or salt form, wherein R is H;
• and (c) alkylating the piperidine nitrogen of the compound of Formula 1I with a suitable alkylating agent to yield the compound of Formula 1J in free or salt form;
• and optionally (d) converting the compound of Formula 1J in free form to a compound of Formula 1J in salt form, e.g., acid addition salt form (e.g., tosylate salt form).