[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([OH:11])[CH:10]=1)[C:5](O)=[O:6].C(Cl)(=O)C(Cl)=O.N.CC[N:21](C(C)C)C(C)C>C(Cl)Cl.CO.CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([OH:11])[CH:10]=1)[C:5]([NH2:21])=[O:6]
A mixture of 3-chloro-5-hydroxybenzoic acid (3.22 mmol), oxalyl chloride (6.5 mmol) and catalytic amount of DMF in DCM was heated at reflux for 2 hrs. (bath temperature at 60° C.). Solvent was evaporated in vacuo and the residue was dissolved in 1,4-dioxane. NH3 (0.5 M in 1,4-dioxane, 1.5 eq.) and DIEA (1.5 eq.) were added and the reaction mixture was stirred at RT overnight. The reaction mixture was transferred to a pressure vessel, followed by the addition of 1 mL of 6 M NH3 in MeOH. The pressure vessel was sealed and heated at 90° C. for 2 hrs. The solvents were evaporated to give a crude product, which was purified by chromatography over silica gel (EtOAc) to yield 0.51 g (57%, theoretical yield 0.896 g) of 3-chloro-5-hydroxybenzamide. LCMS (Cond. A) RT 1.05 min., MH+ 172. 1H NMR (500 MHz, CD3OD) δ 7.31 (t, J=1.7 Hz, 1 H), 7.19 (t, J=1.8 Hz, 1 H), 6.94 (t, J=2.1 Hz, 1 H).
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