Acetic Acid → 2(1H)-Isoquinolinecarboxylic acid, octahydro-4-[(2,2,2-trifluoroacetyl)amino]-, 1,1-dimethylethyl ester

Temperature

2.5 °C

A solution of 2,2,2-trifluoro-N-isoquinolin-4-ylacetamide (1.57 g) and platinum oxide (150 mg) in acetic acid (25 ml) was subjected to hydrogenation (5 atm) at 60° C. for 8 hr. The catalyst was filtered off, and the filtrate was evaporated under reduced pressure. The residue was neutralized with saturated aqueous sodium hydrogen carbonate, and evaporated under reduced pressure. The residue was extracted with THF (30 ml×2), and the extract was dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. THF (25 ml) and diisopropylethylamine (1 g) were added to the residue, and the mixture was cooled to 0 to 5° C. Di-tert-butyl dicarbonate (1.42 g) was added and the mixture was stirred at room temperature for 15 hr. The solvent was evaporated under reduced pressure, and ethyl acetate (50 ml) was added to the residue. Insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The residue was subjected to silica gel column chromatography, and the fraction eluted with hexane-ethyl acetate (9:1-7:3) was concentrated under reduced pressure to give the object compound (1.8 g) as an oil.

1. filtrationThe catalyst was filtered off
2. customthe filtrate was evaporated under reduced pressure
3. customevaporated under reduced pressure
4. extractionThe residue was extracted with THF (30 ml×2)
5. dry with materialthe extract was dried over anhydrous sodium sulfate
6. customThe solvent was evaporated under reduced pressure
7. additionTHF (25 ml) and diisopropylethylamine (1 g) were added to the residue
8. additionDi-tert-butyl dicarbonate (1.42 g) was added
9. customThe solvent was evaporated under reduced pressure, and ethyl acetate (50 ml)
10. additionwas added to the residue
11. filtrationInsoluble material was filtered off
12. concentrationthe filtrate was concentrated under reduced pressure
13. washthe fraction eluted with hexane-ethyl acetate (9:1-7:3)
14. concentrationwas concentrated under reduced pressure

ORD record

ord-e12e845372fc48e498d0b44e1b2002c2

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329691B2