Synthesis of 1,4-diazaspiro[5.5]undecan-3-one

A compound of Formula

• or an acceptable salt thereof;
• wherein
• y is 0, 1, 2, 3, or 4;
• n is 0 or 1;
• R1 is hydrogen, alkyl, or aryl;
• R2 is hydrogen, substituted heteroaryl, or
• R3 is hydrogen, NR5R6, OR7, SR7, or halogen;
• R4 is NR8R9 or OR10;
• R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, aryl, -alkyl-aryl, and —C(O)R11;
• R7 is alkyl, aryl, or -alkyl-aryl;
• R8 and R9 are independently selected from the group consisting of hydrogen, alkyl, aryl, and -alkyl-aryl;
• R10 is alkyl, aryl, or -alkyl-aryl;
• R11 is alkyl or aryl;
• R12 is alkyl, aryl, or -alkyl-aryl;
• and
• R13 is —S-alkyl or Cl;
• each instance of R50 is independently selected from the group consisting of hydrogen, halogen, and alkyl.

A process to prepare a compound of Formula III comprising:

• a. reacting a cyclic ketone with a nitroalkane to afford a cycloalkyl group substituted with nitroalkylene;
• b. reacting the compound of step (a) with a glycinate;
• wherein the cyclic ketone is of Formula:
• wherein the nitroalkane is of Formula:
• wherein the glycinate is of Formula:
• wherein Formula III is:
• wherein
• y is 0;
• n is 0 or 1;
• R1 is hydrogen;
• R2 is hydrogen, substituted heteroaryl, or
• R3 is hydrogen;
• R4 is NR8R9 or OR10;
• R5 and R6 are independently selected from the group consisting of hydrogen, alkyl, aryl, -alkyl-aryl, and —C(O)R11;
• R7 is alkyl, aryl, or -alkyl-aryl;
• R8 and R9 are independently selected from the group consisting of hydrogen, alkyl, aryl, and -alkyl-aryl;
• R10 is alkyl, aryl, or -alkyl-aryl;
• R11 is alkyl or aryl;
• R12 is alkyl, aryl, or -alkyl-aryl;
• R13 is —S-alkyl or Cl.