Ammonia → 3-Chloro-5-hydroxybenzamide

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., MH30 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).

1. temperaturewas heated
2. temperatureat reflux for 2 hrs
3. custom(bath temperature at 60° C.)
4. customSolvent was evaporated in vacuo
5. dissolutionthe residue was dissolved in 1,4-dioxane
6. customThe reaction mixture was transferred to a pressure vessel
7. customThe pressure vessel was sealed
8. temperatureheated at 90° C. for 2 hrs
9. customThe solvents were evaporated
10. customto give a crude product, which
11. customwas purified by chromatography over silica gel (EtOAc)

ORDレコード

ord-a4683c26e7474e4380095f0299edeaa6

出典データセット

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07612069B2