Water → 2-((3-Chloro-2-nitrophenyl)amino)butanoic acid

HRID 75369

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4](F)[C:3]=1[N+:9]([O-:11])=[O:10].[NH2:12][CH:13]([CH2:17][CH3:18])[C:14]([OH:16])=[O:15].C([O-])([O-])=O.[K+].[K+].O>CS(C)=O>[Cl:1][C:2]1[C:3]([N+:9]([O-:11])=[O:10])=[C:4]([NH:12][CH:13]([CH2:17][CH3:18])[C:14]([OH:16])=[O:15])[CH:5]=[CH:6][CH:7]=1

Participants

Conditions

Temperature: 80 °C

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).

Workup

customwent up to 110° C.
temperatureAfter cooling to rt
washThe aq. layer was washed with methyl tert-butyl ether (2×5 L)
customto remove organic impurities
customto give an orange solid
filtrationThe orange solid was collected by filtration
washwashed with water (2×4 L)
customair-dried

Sources & evidence

ORD record: ord-85a071288376462483692b25078970b3
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08835432B2

Linked notes

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