Diisobutylaluminum hydride → tert-Butyl 4-fluoro-8-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate

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Reaction Steps

To a flask containing 2-tert-butyl 8-methyl 4-fluoro-3,4-dihydroisoquinoline-2,8(1H)-dicarboxylate (24-6) (214 mg, 0.692 mmol), was added anhydrous THF (3.5 ml) then cooled to −78 C (dry ice/acetone bath) while stirring under an atmosphere of N2. Then added DIBAL-H (2.4 ml, 2.400 mmol) dropwise. The reaction mixture was then stirred at −78 C for ˜20 minutes, then warmed to room temperature. Followed by LC/MS. After 10 minutes at room temperature quenched by dropwise addition of saturated solution of Rochelle's Salt (Na+/K+ Tartrate) in water, then suspended in EtOAc, washed with saturated NaHCO3, then H2O, then brine; organics dried over Na2SO4, filtered & concentrated. Purification by silica gel chromatography (0-40%; isocratic @ 30% EtOAc/Hex; 24 g ISCO); desired fractions concentrated to yield tert-butyl 4-fluoro-8-(hydroxymethyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate (24-7). HRMS [M+H]; calculated; 282.1500, observed; 282.1491.

Provenance & Evidence