Ethanolamine → N-(2-hydroxyethyl)-3-methoxy-5-nitrobenzamide

Oxalyl chloride (6.4 g; 50.7 mmol; 5 eq) is added to a suspension of 3-nitro-5-methoxy benzoic acid (2 g; 10 mmol; 1 eq) and DMF (cat.) in DCM (50 mL) and the resulting mixture is stirred at room temperature for 1 h then evaporated to dryness. The residue is taken up in THF (20 mL) and added to a solution of ethanolamine (3.1 g; 50.7 mmol; 5 eq) and DIEA (6.6 g; 50.7 mmol; 5 eq) in THF (40 mL). The resulting mixture is stirred at room temperature for 2 h. The solution is evaporated to dryness and the residue partitioned between EtOAc and 0.5 M HCl. The aqueous phase is extracted with EtOAc (3×) and the combined organic layer is washed successively with 0.5 M HCl (2×) then brine (2×). After drying over MgSO4, the solution is concentrated in vacuo to afford a yellow solid. Trituration in a mixture of EtOAc and Et2O followed by filtration afforded 1.35 g (55%) of the title compound as an off-white solid. 1H NMR (DMSO-d6) δ 8.84 (t, J=5.6 Hz, 1H), 8.29 (t, J=1.7 Hz, 1H), 7.86 (d, J=1.7 Hz, 2H), 4.77 (t, J=5.6 Hz, 1H), 3.93 (s, 3H), 3.54 (q, J=5.8 Hz, 2H), 3.35 (q, J=5.6 Hz, 2H), HPLC (max plot) 99%; Rt 1.73 mm.

1. customthen evaporated to dryness
2. stirringThe resulting mixture is stirred at room temperature for 2 h
3. customThe solution is evaporated to dryness
4. customthe residue partitioned between EtOAc and 0.5 M HCl
5. extractionThe aqueous phase is extracted with EtOAc (3×)
6. washthe combined organic layer is washed successively with 0.5 M HCl (2×)
7. dry with materialAfter drying over MgSO4
8. concentrationthe solution is concentrated in vacuo
9. customto afford a yellow solid
10. filtrationfollowed by filtration

ORD record

ord-c4d93dfbdc974ee4940a6eeddee57076

Source dataset

uspto-grants-2013_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08614215B2