4-Oxy-l,2,3,4-tetrahydroisoquinolines

Boc-D-7-hydroxy-l,2,3,4-tetrahydroisoquinoline-3-carboxylic acid was dissolved in THF containing benzotriazol-l-yl-oxy-tris-(dimethylamino)phosphonium hexafluorophosphate and triethylamine and heated with the Step 1 product until amidation was completed. Thereafter, the coupled product was isolated. 

As with the KR processes, the DKR of secondary amines has been explored less than the reactions with primary racemic amines. Ramstrom and coworkers have reported the acylation of l-cyano-l,2,3,4-tetrahydroisoquinoline and 6,7-dimeth-oxy-l,2,3,4-tetrahydroisoquinoline, discovering CAL-B as the best lipase for the acetylation reaction using three equivalents of phenyl acetate as acyl donor (Figure 9.35). The corresponding (S)-amides were obtained in very high enantiomeric excess and quantitative conversion after three days at 40 °C in MTBE [253]. 

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