SYNTHESIS Of DIETHYLPHOSPHONATE

A process for making a compound of the structure of compound 116

• wherein R9 is separately selected for each occurrence from alkyl, aryl, heteroaryl, and arylalkyl groups having 1 to 10 carbon atoms, the process comprising;
• (a) reacting (5-halo-pyridin-2-yl)-methanol of the Formula 137A
• where X2 is selected independently from Cl, Br, or I;
• with an X1 halogenating agent, to produce a compound of the formula of compound 137,
• where X1 is the same for each occurrence and is selected from Cl or Br and X2 is as defined above;
• (b) reacting compound 137 with a phosphite compound of the structure of Formula A,
• wherein R9 is selected from alkyl, aryl, heteroaryl, and arylalkyl groups having 1 to 10 carbon atoms, to produce compound 138,
• wherein R9 is as defined above;
• (c) treating compound 138 with HX3, where X3 is selected from Cl and Br, to precipitate the corresponding hydrohalide salt of Formula 138A,
• wherein R9 is as defined above;
• and
• (d) reacting the hydrohalide salt from step “c” with a 3-fluorophenylboronate compound of the structure of Formula B
• wherein R11 is selected independently for each occurrence from alkyl, aryl heteroaryl and arylalkyl groups having 1 to 10 carbon atoms and hydrogen, optionally in the presence of a palladium catalyst to produce compound 116.

A process for making a compound of the structure of compound 116

• wherein R9 is separately selected for each occurrence from alkyl, aryl, heteroaryl, and arylalkyl groups having 1 to 10 carbon atoms, the process comprising:
• (a) reacting (5-halo-pyridin-2-yl)-methanol of the Formula 137A
• where X2 is selected independently from Cl, Br, or I, with an X1 halogenating agent, to produce a compound of the formula of compound 137,
• where X1 is the same for each occurrence and is selected from Cl or Br and X2 is as defined above;
• (b) reacting compound 137 with a phosphite compound of the structure of Formula A.
• wherein R9 is selected from alkyl, aryl, heteroaryl, and arylalkyl groups having 1 to 10 carbon atoms, to produce compound 138,
• wherein R9 is as defined above;
• (c) treating compound 138 with HX3, where X3 is selected from Cl and Br, to precipitate the corresponding hydrohalide salt of Formula 138A,
• wherein R9 is as defined above;
• and
• (d) reacting the hydrohalide salt from step “c” with an organometallic compound capable of displacing X2 of Formula 138A with a 3-fluorophenyl moiety of Formula B′,
• to produce compound 116.