Acetic Acid → 4-Chloro-2-{[(pyridin-3-yl)methyl]amino}benzoic acid

HRID 1957308Notes

Reaction equation

Cl[C:2]1[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[NH2:12][CH2:13][C:14]1[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+].C(O)(=O)C>CN(C=O)C.O>[Cl:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([NH:12][CH2:13][C:14]2[CH:15]=[N:16][CH:17]=[CH:18][CH:19]=2)[CH:10]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 2,4-dichlorobenzoic acid (10 g, 53 mmol), 3-aminomethylpyridine (4.5 ml, 44 mmol), K2CO3 (7.8g, 56 mmol) and CuBr (80 mg, cat) in DMF (20 ml) was heated at 150° C. for 1 hour, cooled to 0° C., diluted with water (80 ml) and carefully acidified with glacial acetic acid. The resulting solid was collected by filtration, washed with water, acetone and ether to give the pure product (>99% by HPLC) as a bluish white solid (3.46 g, 30%), m.p. 235°-236° C.; 1H NMR d (DMSO, 360 MHz, 353 K) 8.60 (bs, 1H, aromatic), 8.49 (bs, 1H, aromatic), 7.79 (d, J=8.5 Hz, 1H, aromatic), 7.72 (d, J=7.8 Hz, 1H, aromatic), 7.35 (dd, J=4.8, 7.6 Hz, 1H, aromatic), 6.74 (d, J=1.8 Hz, 1H, aromatic), 6.59 (dd, J=2.0, 8.4 Hz, 1H, aromatic), 4.51 (s, 2H, CH2); HRMS [M-2H]- calcd for C13 H9N2O2Cl: 260.0353. Found: 260.0348. Anal. calcd for C13H11ClN2O2.1/4H2O: C, 58.44; H, 4.33; N, 10.48. Found: C, 58.30; H, 4.10; N, 10.25.

Workup

temperaturecooled to 0° C.
filtrationThe resulting solid was collected by filtration
washwashed with water, acetone and ether

Sources & evidence

ORD record: ord-94638d03c02245a2917b26adeb70163d
Source dataset: uspto-grants-1998_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05783698

Reaction notes

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