[CH2:1]([Mg]Br)[C:2]([CH3:5])([CH3:4])[CH3:3].[Cl:8]CCl.C(OC(=O)[NH:17][CH:18]1[C:27]2[C:22](=[CH:23][CH:24]=[C:25](Br)[CH:26]=2)[CH2:21][O:20][CH2:19]1)(C)(C)C.Cl>[Cl-].[Zn+2].[Cl-]>[ClH:8].[CH3:3][C:2]([CH3:5])([CH3:4])[CH2:1][C:25]1[CH:26]=[C:27]2[C:22](=[CH:23][CH:24]=1)[CH2:21][O:20][CH2:19][CH:18]2[NH2:17]
Neo-pentylmagnesium bromide (10 mL, 9.1 mmol, 1.0 M in ether) was added dropwise to a solution of zinc chloride (18.2 mL, 0.5 M in tetrahydrofuran, 9.1 mmol) over 0.5 h and the reaction mixture stirred at RT for an additional 0.5 h. [1,1′-Bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (250 mg, 0.30 mmol) was added to the reaction mixture followed by (6-Bromo-isochroman-4-yl)-carbamic acid tert-butyl ester (1.00 g, 3.04 mmol) and the reaction mixture heated at reflux for 1 h. The reaction mixture was cooled and then concentrated under reduced pressure. The residue was re-dissolved in ethyl acetate and washed with water, sodium chloride, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography over silica (83:17 hexanes/ethyl acetate) yielded the desired protected amine (303 mg, 31%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.30–7.23 (m, 1H), 7.00 (d, J=6.3 Hz, 1H), 6.74 (s, 1H), 5.09–5.06 (m, 1H), 4.79–4.65 (m, 3H), 4.13–3.85 (m, 2H), 2.45 (s, 2H), 1.46 (s, 9H), 0.89 (s, 9H); ESI MS m/z 320 [C19H29NO3+H]+. A solution of protected amine (303 mg, 0.95 mmol) in hydrogen chloride (20 mL, 4 N in 1,4-dioxane, 80 mmol) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure to give 6-(2,2-Dimethyl-propyl)-isochroman-4-ylamine hydrochloride (210 mg, quantitative) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.28 (d, J=7.6 Hz, 1H), 7.01 (d, J=7.6, 1.2 Hz, 1H), 6.73 (d, J=1.2 Hz, 1H), 4.75 (ABq, J=15.0 Hz, 2H), 3.96–3.80 (m, 3H), 2.44 (s, 2H), 1.73 (m, 2H), 0.89 (s, 9H); ESI MS m/z 220 [C14H21NO+H]+.
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