Diisopropylethylamine → (2S)-N-((1R)-2-azido-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide

A solution of (1R)-2-azido-1-(4-(2-methylpentyloxy)phenyl)ethanamine (9.0 g, 34.3 mmol) in dichloromethane (100 mL) was cooled to 0° C. To this solution, (S)-2-phenylpropanoic acid (7.0 mL, 51.5 mmol), N,N-diisopropylethylamine (35.9 mL, 206 mmol) and HATU (19.57 g, 51.5 mmol) were added. The ice bath was removed and reaction mixture was stirred at room temperature for 3 h. The reaction mixture was transferred to a separatory funnel containing saturated aqueous NaHCO3 solution (60 mL). The aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (25 mL), dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (30→40% ethyl acetate in hexanes) to afford (2S)-N-((1R)-2-azido-1-(4-(2-methylpentyloxy)phenyl)ethyl)-2-phenylpropanamide (12.5 g, 92% yield) as a colorless solid: 1H NMR (400 MHz, CDCl3) δ 7.21-7.34 (m, 5H), 6.98 (d, J=8.6 Hz, 2H), 6.78 (d, J=8.8 Hz, 2H), 6.37 (d, J=8.1 Hz, 1H), 5.10 (ddd, J=7.9, 5.8, 5.7 Hz, 1H), 3.76 (dd, J=9.1, 5.8 Hz, 1H), 3.61-3.70 (m, 2H), 3.46-3.56 (m, 2H), 1.87-1.98 (m, 1H), 1.52 (d, J=7.3 Hz, 3H), 1.26-1.51 (m, 3H), 1.21 (dddd, J=12.3, 7.6, 5.3, 5.0 Hz, 1H), 1.01 (d, J=6.5 Hz, 3H), 0.93 (t, J=7.1 Hz, 3H); LRMS (ESI) m/e 395.3 [(M+H)+, calcd for C23H31N4O2 395.3].

1. customThe ice bath was removed
2. customreaction mixture
3. customThe reaction mixture was transferred to a separatory funnel
4. extractionThe aqueous layer was extracted with ethyl acetate (3×50 mL)
5. washThe combined organic layers were washed with brine (25 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by column chromatography on silica gel (30→40% ethyl acetate in hexanes)

ORD record

ord-90f7a5b9371f4106bc815229ef8db33e

Source dataset

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08304577B2