Reaction #162551

Reaction equation

water

1-chloro-3-fluoro-2-nitrobenzene

2-aminobutyric acid

K2CO3

→

2-((3-chloro-2-nitrophenyl)amino)butanoic acid

Yield 96.7%

Solvents

DMSO

Conditions

Workup

1. 1
   Otherwent up to 110° C.
2. 2
   TemperatureAfter cooling to rt
3. 3
   WashThe aq. layer was washed with methyl tert-butyl ether (2×5 L)
4. 4
   Otherto remove organic impurities
5. 5
   Otherto give an orange solid
6. 6
   FiltrationThe orange solid was collected by filtration
7. 7
   Washwashed with water (2×4 L)
8. 8
   Otherair-dried

Procedure

A mixture of 1-chloro-3-fluoro-2-nitrobenzene (2.00 Kg, 11.4 mol), 2-aminobutyric acid (1.22 kg, 11.8 mol) and K2CO3 (1.58 Kg, 11.4 mol) in anhydrous DMSO (4.2 L) was heated at 80° C. for 16 h (after the reaction initiated, the internal temperature went up to 110° C.). At this time LC-MS analysis showed that the reaction was complete. After cooling to rt, the reaction mixture was carefully poured into water (10 L) with vigorous stirring. The aq. layer was washed with methyl tert-butyl ether (2×5 L) to remove organic impurities. The aq. layer was then acidified to pH ˜1.5 with cond HCl to give an orange solid. The orange solid was collected by filtration, washed with water (2×4 L) and air-dried to give 2-((3-chloro-2-nitrophenyl)amino)butanoic acid (2.85 Kg), which was used as such in the next step. 1H NMR (DMSO-d6) δ ppm 7.35 (t, J=8.3 Hz, 1H), 6.82-6.91 (m, 2H), 6.25 (d, J=7.6 Hz, 1H), 4.14 (td, J=7.4, 5.4 Hz, 1H), 3.4 (br. s., 1H), 1.74-1.92 (m, 2H), 0.88 (t, J=7.4 Hz, 3H). Mass Spectrum (ESI) m/z=259.2 (M+1).

Source