2-Amino-2-methyl-1-propanol → (2S,3S)-2-(3-bromophenyl)-3,5,5-trimethylmorpholin-2-ol

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Reaction Steps

Compound 4d was synthesized by a procedure similar to that described for (2S,3S)-4a using (R)-1-(3-bromophenyl)-2-hydroxypropan-1-one (10d, 4.0 g, 0.018 mol), Proton sponge (4.5 g, 0.021 mol), triflic anhydride (3.2 mL, 192 mmol), and 2-amino-2-methyl-1-propanol (3.4 g, 0.038 mol) in acetonitrile (50 mL). After purification, 2.04 g (39%) of the free base 4d was isolated and converted to 1.6 g of the hemi-D-tartrate salt, which had >99% ee: mp 129-130° C.; [α]20D +9.6° (c 1.0, CH3OH); 1H NMR (methanol-d4) δ 7.77-7.76 (m, 1H), 7.63-7.53 (m, 2H), 7.38-7.32 (m, 1H), 4.37 (s, 1H), 4.14 (d, 1H, J=12.0 Hz), 3.58-3.39 (m, 2H), 1.57 (s, 3H), 1.32 (s, 3H), 1.07-1.02 (m, 3H); 13C NMR (methanol-d4) δ 178.8, 145.1, 133.3, 131.1, 126.9, 123.6, 96.7, 75.2, 67.7, 55.0, 24.4, 21.5, 14.4; LCMS (ESI) m/z 300.6 [(M-tartrate)+, M=C15H21BrNO5]; Anal. (C15H21BrNO5.0.25H2O) calcd: C, 47.44; H 5.71; N, 3.69. found: C, 47.33; H, 5.84; N, 3.63.

Provenance & Evidence