Formic Acid → 4-Oxoadamantane-1-carboxylic acid

Temperature

80 °C

To 60% fuming sulfuric acid (135 ml) stirred under heating at 80° C., a solution of 4-oxoadamantan-1-ol (15.69 g) in formic acid (250 ml) was added dropwise over 2 hours. After completion of the dropwise addition, the reaction mixture was stirred at 80° C. for 3 hours, to which formic acid (100 ml) was then added at room temperature and stirred overnight at room temperature. After addition of additional formic acid (50 ml), the reaction mixture was stirred at 80° C. for 12 hours and then stirred overnight at room temperature. The reaction mixture was poured into ice-cold water, filtered to remove insoluble materials and then extracted three times with toluene. After the combined organic layers were extracted with 4M aqueous sodium hydroxide, the aqueous layer was washed three times with chloroform. The aqueous layer was adjusted to pH 1 to 2 by addition of 12M aqueous hydrochloric acid and then extracted with chloroform. The organic layer was washed with brine and then dried over anhydrous sodium sulfate. After the desiccant was filtered off, the solvent was distilled off under reduced pressure to give 4-oxoadamantane-1-carboxylic acid (9.84 g) as a colorless powder. To a solution of 4-oxoadamantane-1-carboxylic acid thus obtained (1.50 g) in 8M ammonia/methanol (30 ml), 10% palladium on activated carbon (150 mg) was added and stirred overnight under a hydrogen atmosphere at room temperature. After addition of water (10 ml), the reaction mixture was filtered through celite and washed with methanol, and the filtrate was concentrated under reduced pressure. To the resulting crystal, acetonitrile (30 ml) was added and stirred at room temperature for 3 hours. The crystal was collected by filtration to give 4-aminoadamantane-1-carboxylic acid (1.28 g) as a colorless powder. To a solution of 4-aminoadamantane-1-carboxylic acid thus obtained (1.28 g) in methanol (13 ml), acetyl chloride (2.34 ml) was added under ice cooling and stirred at room temperature for 20 minutes and then at 45° C. for 8 hours. The reaction mixture was stirred overnight at room temperature and then further stirred at 45° C. for 4 hours. After the reaction mixture was cooled to room temperature and then concentrated, the resulting crystal was dissolved in chloroform and filtered through celite. The filtrate was concentrated under reduced pressure, and the residue was converted into a powder form by addition of acetonitrile (10 ml). The crystal was collected by filtration and washed sequentially with acetonitrile and n-hexane to give the titled compound, i.e., methyl 4-aminoadamantane-1-carboxylate (1.22 g) as a colorless powder.

1. additionAfter completion of the dropwise addition
2. additionwas then added at room temperature
3. stirringthe reaction mixture was stirred at 80° C. for 12 hours
4. stirringstirred overnight at room temperature
5. additionThe reaction mixture was poured into ice-cold water
6. filtrationfiltered
7. customto remove insoluble materials
8. extractionextracted three times with toluene
9. extractionAfter the combined organic layers were extracted with 4M aqueous sodium hydroxide
10. washthe aqueous layer was washed three times with chloroform
11. additionThe aqueous layer was adjusted to pH 1 to 2 by addition of 12M aqueous hydrochloric acid
12. extractionextracted with chloroform
13. washThe organic layer was washed with brine
14. dry with materialdried over anhydrous sodium sulfate
15. filtrationAfter the desiccant was filtered off
16. distillationthe solvent was distilled off under reduced pressure

ORD record

ord-431598c1a8f044bc8ddaf5c35b860b03

Source dataset

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08222417B2