N-Formylmorpholine → Tert-butyl 5-formyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

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Reaction Steps

A solution of 5-bromo-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 19a (3.87 g, 12.39 mmol) in diethyl ether (60 mL) was cooled to −100° C. A solution of 1.7 M tert-butyllithium in hexanes (16.04 mL, 27.27 mmol) was added dropwise. After the addition, stirring was continued for 30 min to −100° C. 4-Formylmorpholine (1.87 mL, 18.59 mmol) in diethyl ether (10 mL) was added all at once and the reaction was stirred for an additional 1 h. The mixture was then allowed to reach room temperature. Ammonium chloride saturated solution was added and the product was extracted with dichloromethane (3×70 mL). The combined organics were dried with magnesium sulfate, the solvent was evaporated and the residue was purified by flash chromatography eluting with 20% ethyl acetate in hexanes, to yield 0.44 g of 5-formyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester 20a.

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