Sodium hydride → HCID 10134015, compound

Participants

Reaction Steps

To a round-bottom flask, equipped with stir bar and septum, is placed 6-hydroxy-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (1 g, 4.01 mmol), KI (599 mg, 4.01 mmol) and NaH (162 mg, 95% dry, 6.42 mmol). Then, dry DMF (20 mL, 0.5 M) is added via syringe followed by N-(3-chloropropyl)piperidine (0.85 mL, 5.2 mmol). The reaction is allowed to stir at 70 degrees overnight. In the morning, the reaction is quenched with water, extracted into EtOAc (3×20 mL) and dried over brine. Column chromatography in 9:1 DCM:MeOH affords 6-(3-piperidin-1-yl-propoxy)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester an orange oil (1 g, 67%). Mass sec hit M+1, 375; LCMS>95% @230 nm and ELSD. In a similar manner the Examples 35, 139, and 164 are prepared:

Provenance & Evidence