Dimethylformamide → Ethyl 2-azabicyclo[2.2.1]heptane-3-carboxylate

To a solution of 2-(4-methoxybenzyl)-2-azabicyclo[2.2.1]heptane-3-carboxylic acid (297 mg, 1.14 mmol) in dichloromethane (4.4 ml) were added oxalyl chloride (0.21 ml, 2.34 mmol) and N,N-dimethylformamide (0.09 ml, 1.14 mmol) while being cooled with ice, and the mixture was stirred at room temperature for 30 minutes. Separately, to a suspension of hydroxylamine hydrochloride (316 mg, 4.55 mmol) in tetrahydrofuran (1.5 ml)-water (0.3 ml) was added triethylamine (0.97 ml, 6.94 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 15 hours. The reaction mixture, with water added thereto, was extracted with ethyl acetate. 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% methanol/chloroform), to give the entitled compound (152 mg, 47% 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 15 hours
4. extractionwas extracted with ethyl acetate
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% methanol/chloroform)

ORD record

ord-994af23da4b247e4b60621db5166a6f8

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07176217B2