Sodium Sulfate → N-(4-Bromo-2-(2,2-dimethoxyethyl)phenyl)tetrahydro-2H-pyran-4-amine

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Reaction Steps

Compound 67 (300 mg, 1.153 mmol) and dihydro-2H-pyran-4(3H)-one (231 mg, 2.306 mmol) were stirred in acetic acid (10 mL) under Argon in the presence of anhydrous sodium sulfate (1.638 g, 11.530 mmol) at room temperature for 30 minutes. Sodium triacetoxyborohydride (733 mg, 3.459 mmol) was then added and the mixture stirred for 19 hours at room temperature. After dilution with a mixture of 8:1 ethyl acetate:Hexanes, the reaction is quenched with saturated sodium bicarbonate. The mixture was transferred to a separatory funnel and the organic layer separated. The organic layer was dried over sodium sulfate and concentrated under reduced pressure and the residue purified via chromatography on silica gel (EtOAc: Hexanes, 1:4 then 2M NH3 in methanol:CH2Cl2, 3:7 then 100% methanol) to yield a pale yellow oil, 87 (168 mg, 42.3%). 1H NMR (DMSO-d6) δ 1.34-1.47 (m, 2H), 1.86 (d, 2H, J=12.3 Hz), 2.75 (d, 2H, J=5.3 Hz), 3.27 (s, 6H), 3.35-3.49 (2×m, 3H), 3.77-3.91 (2×m, 2H), 4.52 (t, 1H, J=5.3 Hz), 4.89 (d, 1H, J=7.6 Hz), 6.60 (d, 1H, J=9.4 Hz), 7.10-7.20 (m, 2H); ESI-MS (m/z, %): 344/346 (MH+, 5%), 280/282 (cyclized product, 100%).

Provenance & Evidence