合成路线1

In this scheme various methods are shown for the synthesis of (S)-atenolol: 1. Treatment of (R)-glycidyl 4-nitrobenzenesulfonate (I) with HCl (either concentrated or with dichloromethane) provides 3-chloropropyl derivative (II), which is then coupled with isopropylamine (III) in dichloromethane to afford 3-chloropropylisopropylamine (IV). Finally, condensation of (IV) with 2-(4-hydroxyphenyl)acetamide (V) by means of KOH in MeOH gives the desired product. Alternatively, derivative (IV) can be converted into (S)-atenolol by its condensation with 2-(4-hydroxy-phenyl)acetonitrile (VI) by means of KOH to yield compound (VII), followed by hydrolysis with HCl at 40 C. 2. Condensation of (R)-glycidyl 3-nitrobenzenesulfonate (VIII) with isopropylamine (III) followed by coupling with acetamide (V) by means of potassium tert-butylate in DMSO provides the desired product. 3. Treatment of (VIII) with HCl affords 2(S)-hydroxy-3-chloropropyl-3-nitrobenzenesulfonate (IX), which is first coupled with isopropylamine (III) to give (IV) and finally condensed with amide (V). 4. Coupling of chloro derivative (IX) with benzyl-protected isopropylamine (X) provides protected derivative (XI), which is then condensed with acetamide (V) by means of KOH in MeOH to give (XII). Finally, compound (XII) is hydrogenated over Pd/C in MeOH for removal of the benzyl group.