Hydrochloric Acid → Ethyl 2-azabicyclo[2.2.1]heptane-3-carboxylate

To a solution was 2-(4-methoxybenzoyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (217 mg, 0.787 mmol) in dichloromethane (3.0 ml) were added oxalyl chloride (0.14 ml, 1.65 mmol) and N,N-dimethylformamide (0.06 ml, 0.787 mmol) while being cooled with ice, and the mixture was stirred at room temperature for 30 minutes. Separately, to a suspension of hydroxylamine hydrochloride (219 mg, 3.15 mmol) in tetrahydrofuran (1.0 ml)-water (0.2 ml) was added triethylamine (0.67 ml, 4.80 mmol) at 0° C., and the mixture was stirred at 0° C. for 15 minutes. To this reaction mixture was added the acid chloride solution at 0° C., and the mixture was stirred at room temperature for 4 hours. The reaction mixture was acidified with 1N hydrochloric acid and extracted with chloroform. The organic layer was washed with saturated brine and dried over magnesium sulfate. The solvent was evaporated, and the resulting residue was purified by silica gel column chromatography (2.5%–10% methanol/chloroform), to give the entitled compound (69.4 mg, 30% through the two steps of (b) and (c)).

1. temperaturewhile being cooled with ice
2. stirringthe mixture was stirred at 0° C. for 15 minutes
3. stirringthe mixture was stirred at room temperature for 4 hours
4. extractionextracted with chloroform
5. washThe organic layer was washed with saturated brine
6. dry with materialdried over magnesium sulfate
7. customThe solvent was evaporated
8. customthe resulting residue was purified by silica gel column chromatography (2.5%–10% methanol/chloroform)

ORD record

ord-7d012ccc1bab4cdfa41a8647e2ba9044

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07176217B2