New Process for the Preparation of Fluoropyrrolidine

A process for the preparation of a compound of formula (I),

• or an acceptable salt thereof, comprising the following steps:
• (a) the reaction of a compound of formula (B1) or (B1′)
• with a compound of formula (B2)
• in presence of a suitable solvent (i) and in presence of a suitable base (i), to arrive at a compound of formula (C1′)
• (b) the reaction of the compound of formula (C1) with a compound of formula (C2′)
• in presence of a suitable base (ii) and a suitable solvent (ii), to arrive at a compound of formula (D1′)
• (c) the reaction of the compound of formula (D1′) with a suitable fluorination agent in presence of a suitable solvent (iii) and optionally a suitable base (v), to arrive at a compound of formula (E1)
• (d) the reaction of the compound of formula (E1) with a suitable acid (i) and a suitable solvent (iv), to arrive at a compound of formula (I) or an acceptable salt thereof.

A process for the preparation of a compound of formula (I),

• or an acceptable salt thereof, comprising the following steps:
• (a) the reaction of a compound of formula (A1)
• in presence of a suitable solvent (v) and in presence of H2, a suitable catalyst, ammonia and ammonium chloride;
• (b) adding a suitable base (iv) in a suitable solvent (vi) to arrive at the compound of formula (B1)
• (c) optionally:
• (1) isolate the crude product of the compound of formula (B1) from the reaction mixture by means of distillation;
• (2) dissolving the crude product of a compound of formula (B1) in a suitable solvent (vii);
• and (3) isolate the crude product of the compound of formula (B1)) from the reaction mixture by means of distillation;
• (d) the reaction of a compound of formula (B1)
• with a compound of formula (B2)
• in presence of a suitable solvent (i), to arrive at a compound of formula (C1′)
• (e) the reaction of the compound of formula (C1) with a compound of formula (C2′)
• in presence of a suitable base (ii) and a suitable solvent (ii), to arrive at a compound of formula (D1′)
• (f) the reaction of the compound of formula (D1′) with a suitable fluorination agent in presence of a suitable solvent (iii) and a suitable base (v), to arrive at a compound of formula (E1)
• (g) the reaction of the compound of formula (E1) with a suitable acid (i) and a suitable solvent (iv), to arrive at a compound of formula (I) or an acceptable salt thereof.

A process for the preparation of a compound of formula (B1),

• or an acceptable salt thereof, comprising the following steps:
• (a) the reaction of a compound of formula (A1)
• in presence of a suitable solvent (v) and in presence of H2, a suitable catalyst, ammonia and ammonium chloride;
• (b) adding a suitable base (iv) in a suitable solvent (vi) to arrive at the compound of formula (B1), or an acceptable salt thereof
• (c) isolate the crude product of the compound of formula (B1), or an acceptable salt thereof, from the reaction mixture by means of distillation;
• and optionally further comprising the following steps:
• (d) dissolving the crude product of a compound of formula (B1), or an acceptable salt thereof, in a suitable solvent (vii);
• and
• (e) isolate the crude product of the compound of formula (B1)), or an acceptable salt thereof, from the reaction mixture by means of distillation.