Dimethyl Sulfide → (3RS,4S)-2,2-dimethyl-4-(trityl-amino)-hexan-3-ol

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Reaction Steps

To a stirred suspension of CuBr.SMe2 (1.37 g, 2.2 eq, 6.66 mmol) in ether (100 mL) under an argon atmosphere at −78° C., was added tert-butyl lithium (1.5 M in pentane, 8.0 mL, 4 eq, 12.0 mmol) dropwise and the solution allowed to warm to room temperature. The mixture was recooled to −55° C., to which was added a solution of (S)-2-(trityl-amino)-butyraldehyde (1 g, 1 eq, 3.03 mmol) in ether (25 mL) dropwise with stirring, and stirred at this temperature for 3 h. To the reaction mixture was added a saturated aqueous solution of NH4Cl (100 mL) and allowed to warm to room temperature over 16 h. The reaction mixture was extracted with ether (2×200 mL), and the combined organic phase washed with brine (50 mL), dried (MgSO4) and evaporated in vacuo. The residue was purified by silica gel column chromatography, eluted with hexane:ether (100:0→90:10) to afford the title compound as a light yellow oil; Yield: 0.47 g (40%). (53% de 3R,4S: 47% de 3S,4S) 1H-NMR (d6-DMSO, 250 MHz): δ 0.37+0.87 (2×t, 3H, J=7.46 Hz, —NHCH(CH2CH3)CH(C(CH3)3)OH), 0.58+0.71 (2×s, 9H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 1.38-1.52 (m, 2H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 2.00 (m, 1H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 2.28 (m, 1H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 2.95 (m, 1H, —NHCH(CH2CH3)CH(C(CH3)3)OH), 4.24+4.79 (2×d, 1H, J=5.21+6.16 Hz, —NHCH(CH2CH3)CH(C(CH3)3)OH), 7.15-7.53 (m, 15H, 3×Bz).

Provenance & Evidence