The condensation of 4-fluorobenzaldehyde (I) with 4-methyl-3-oxopentanoic acid ethyl ester (II) by means of piperidine/AcOH in refluxing benzene gives the corresponding benzylidene derivative (III), which is cyclized with S-methylisothiourea (IV) and oxidized with DDQ, affording the pyrimidine derivative (V). The oxidation of (V) with m-chloroperbenzoic acid (m-CPBA) gives the expected methanesulfonyl derivative (VI), which is treated first with methylamine and then with methanesulfonyl chloride to provide the N-methylmethanesulfonamide (VII). The reduction of the ester group of (VII) with DIBAL in toluene, followed by selective oxidation of the resulting alcohol with TPAP, affords the aldehyde (VIII), which is submitted to a Wittig condensation with the phosphorane (IX) in acetonitrile to give the protected heptenoate (X). The deprotection of (X) with FH and the controlled reduction of the resulting keto alcohol with Et2BOMe and NaBH4 affords the chiral dihydroxyheptenoate (XI), which is hydrolyzed with NaOH in ethanol, yielding the corresponding sodium salt (XII). Finally, this compound is treated with calcium chloride.

The condensation of 4-fluorobenzaldehyde (I) with 4-methyl-3-oxopentanoic acid ethyl ester (II) by means of piperidine/AcOH in refluxing benzene gives the corresponding benzylidene derivative (III), which is cyclized with S-methylisothiourea (IV) and oxidized with DDQ, affording the pyrimidine derivative (V). The oxidation of (V) with m-chloroperbenzoic acid (m-CPBA) gives the expected methanesulfonyl derivative (VI), which is treated first with methylamine and then with methanesulfonyl chloride to provide the N-methylmethanesulfonamide (VII). The reduction of the ester group of (VII) with DIBAL in toluene, followed by selective oxidation of the resulting alcohol with TPAP, affords the aldehyde (VIII), which is submitted to a Wittig condensation with the phosphorane (IX) in acetonitrile to give the protected heptenoate (X). The deprotection of (X) with FH and the controlled reduction of the resulting keto alcohol with Et2BOMe and NaBH4 affords the chiral dihydroxyheptenoate (XI), which is hydrolyzed with NaOH in ethanol, yielding the corresponding sodium salt (XII). Finally, this compound is treated with calcium chloride.

The condensation of 4-fluorobenzaldehyde (I) with 4-methyl-3-oxopentanoic acid ethyl ester (II) by means of piperidine/AcOH in refluxing benzene gives the corresponding benzylidene derivative (III), which is cyclized with S-methylisothiourea (IV) and oxidized with DDQ, affording the pyrimidine derivative (V). The oxidation of (V) with m-chloroperbenzoic acid (m-CPBA) gives the expected methanesulfonyl derivative (VI), which is treated first with methylamine and then with methanesulfonyl chloride to provide the N-methylmethanesulfonamide (VII). The reduction of the ester group of (VII) with DIBAL in toluene, followed by selective oxidation of the resulting alcohol with TPAP, affords the aldehyde (VIII), which is submitted to a Wittig condensation with the phosphorane (IX) in acetonitrile to give the protected heptenoate (X). The deprotection of (X) with FH and the controlled reduction of the resulting keto alcohol with Et2BOMe and NaBH4 affords the chiral dihydroxyheptenoate (XI), which is hydrolyzed with NaOH in ethanol, yielding the corresponding sodium salt (XII). Finally, this compound is treated with calcium chloride.