Diisopropylethylamine → tert-butyl (3S)-3-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

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Reaction Steps

A solution of (S)-3,4-dihydro-1H-isoquinoline-2,3-dicarboxylic acid 2-tert-butyl ester (1.0 g, 3.61 mmol) in THF (20 mL) is stirred at RT for 10 min. HATU (1.51 g, 3.97 mmol) is added and the suspension is allowed to stir at RT for 30 min. To the solution is added iPr2NEt (1.57 mL, 9.02 mmol) and the mixture is allowed to stir at RT for 18 h. NaBH4 is added (0.164 g, 4.33 mmol) then the mixture is quenched with MeOH (1 mL), extracted with EtOAc (2×30 mL), washed with 1N HCl (4×50 mL), saturated NaHCO3 (2×50 mL) and brine (2×50 mL). The organic layer is dried over Na2SO4 and concentrated. The residue is purified by column chromatography, eluting with a gradient of 20-50% EtOAc/hexane as eluent to afford the title compound.

Provenance & Evidence