Methanol → (S)-methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate

Temperature

0 °C

To a solution of (S)-2-amino-3-(4-(tert-butoxycarbonyl)phenyl)propanoic acid (500.0 mg, 1.88 mmol) in MeOH (20 mL) at 0° C. was slowly added thionyl chloride (447.64 mg, 3.77 mmol). The reaction was stirred for 1 h at 0° C. then warmed to RT and stirred for 1 h. The solvent was removed under reduced pressure. The reaction mixture was washed with saturated aqueous NaHCO3 (20 ml) and extracted with DCM (3×10 ml). The organic layer was dried over MgSO4 and concentrated. The crude product was purified by chromatography (EA/hexanes) to afford 425 mg (95%) of (S)-methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate as the HCl salt. LCMS-ESI (m/z) calculated for C12H15NO4: 237.1. found 238.0 [M+H]+, tR=1.01 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 8.55 (s, 3H), 7.94 (d, J=8.3 Hz, 2H), 7.41 (d, J=8.3 Hz, 2H), 4.37 (t, J=6.8 Hz, 1H), 3.86 (s, 3H), 3.68 (s, 3H), 3.20 (dd, J=11.8, 6.8 Hz, 2H).

1. customat 0° C.
2. temperaturethen warmed to RT
3. stirringstirred for 1 h
4. customThe solvent was removed under reduced pressure
5. washThe reaction mixture was washed with saturated aqueous NaHCO3 (20 ml)
6. extractionextracted with DCM (3×10 ml)
7. dry with materialThe organic layer was dried over MgSO4
8. concentrationconcentrated
9. customThe crude product was purified by chromatography (EA/hexanes)

ORD record

ord-5d4daac288f049bdb43c64a30309277d

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09187522B2