4-MORPHOLIN-4-YL-PYRIDINE-2-CARBOXYLIC ACID X HCL synthesis

Yield:1431470-39-1 40%

Reaction Conditions:

Stage #1: 4-morpholin-4-yl-pyridine-2-carboxylic acid hydrochloridewith oxalyl dichloride;N,N-dimethyl-formamide in dichloromethane at 0 - 20;
Stage #2: O-(tert-butyl)hydroxylamine hydrochloridewith triethylamine in dichloromethane at 20; for 20 h;

Steps:

110.1 Example 1104-Morpholin-4-yl-pyridine-2-carboxylic acid hydroxyamide Step 1

Step 1
Oxalyl chloride (0.11 mL, 1.3 mmol, 1.3 eq) was added drop wise to a solution of 4-morpholin-4-yl-pyridine-2-carboxylic acid hydrochloride (240 mg, 1.0 mmol, 1 eq) in dichloromethane (10 mL).
At 0° C., dimethylformamide (2-3 drops) was added drop wise and the mixture was stirred at room temperature for 15 min and was evaporated to dryness.
The residue was diluted in dichloromethane (10 mL) and triethylamine (0.41 mL, 2.9 mmol, 3 eq) and O-tert-butylhydroxylamine hydrochloride (185 mg, 1.5 mmol, 1.5 eq) were added.
After stirring at room temperature for 20 h, the mixture was absorbed on silica gel to be purified using cyclohexane and ethyl acetate (100/0 to 0/100).
4-Morpholin-4-yl-pyridine-2-carboxylic acid tert-butoxy-amide was obtained as a white powder (110 mg, 40% yield).

References:

US2013/102600,2013,A1 Location in patent:Paragraph 0634-0635