Reaction Steps
To 365 mg (0.71 mmol) of tert-butyl (1S,2R)-3-{[1-(3-bromophenyl)-1-methylethyl]amino}-1-(3,5-difluorobenzyl)-2-hydroxypropylcarbamate 30 in 2 mL of CH2Cl2 is added 1 mL of trifluoroacetic acid, and the mixture is stirred for 30 min. It is concentrated in vacuo, diluted with ethyl acetate, and washed with 10% Na2CO3 and then brine. The solution is dried over Na2SO4, filtered and concentrated to a colorless oil. This is dissolved in 3 mL of CH2Cl2 and 172 mg (1.56 mmol) of acetyl imidazole is added. After 2.5 h the mixture is concentrated and taken up in ethyl acetate and 1 N KH2PO4. The organic phase is washed with 1N KH2PO4, with brine, dried over Na2SO4, concentrated, and chromatographed over silica gel. Elution with 4% methanol (containing 1% of NH4OH) in CH2Cl2 affords a sticky solid. This is dissolved in ether and treated with ethereal HCl. Concentration afford 260 mg (0.49 mmol, 68%) of compound 31 as a white solid: 1H NMR (CDCl3+CD3OD drop) δ 7.79 (n m, 1 H), 7.59 (m, 2 H), 7.36 (t, J=8 Hz, 1 H), 6.69-6.62 (m, 3 H), 5.15 (m, 1 H), 4.17 (m, 1 H), 3.07 (d, J=12.5 Hz, 1 H), 2.87-2.75 (m, 2 H), 2.61 (dd, J=7, 13.5 Hz, 1 H), 2.21 (s, 3 H), 1.95 (s, 3 H), 1.92 (s, 3 H), 1.84 (s, 3 H); IR (diffuse reflectance) 2985, 2958, 2940, 2755, 2738, 2730, 1749, 1645, 1628, 1596, 1569, 1463, 1372, 1227, 1118 cm −1. MS (CI)m/z(rel intensity) 497 (MH+, 86), 500 (15), 499 (99), 497 (86), 419 (28), 283 (18), 231 (22), 136 (17), 77 (46), 60 (13), 58 (18). HRMS (ESI) calcd for C23H27N2O3F2Br+H1 497.1252, found 497.1248.
