Acetic Acid → Tert-butyl [2-fluoro-5-(methylamino)phenyl]carbamate

To a solution of the above-mentioned crude product of tert-butyl [2-fluoro-5-(formylamino)phenyl]carbamate in tetrahydrofuran (100 mL) was added borane dimethylsulfide complex (11.7 mL, 111 mmol), and the mixture was stirred at room temperature for 1.5 hr. To the reaction mixture were successively added methanol (20 mL) and acetic acid (10 mL), and the mixture was stirred at room temperature for 30 min. The reaction mixture was concentrated under reduced pressure. To the obtained residue was added saturated aqueous sodium hydrogen carbonate solution (100 mL), and the mixture was extracted with ethyl acetate (100 mL, 30 mL). The combined organic layer was washed with saturated brine (20 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0→90/10), and the fractions containing the object product were concentrated under reduced pressure to give the title compound (7.80 g, 73%) as a yellow oil.

1. stirringthe mixture was stirred at room temperature for 30 min
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. additionTo the obtained residue was added saturated aqueous sodium hydrogen carbonate solution (100 mL)
4. extractionthe mixture was extracted with ethyl acetate (100 mL, 30 mL)
5. washThe combined organic layer was washed with saturated brine (20 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationThe insoluble material was filtered off
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=100/0→90/10)
10. additionthe fractions containing the object product
11. concentrationwere concentrated under reduced pressure

ORD record

ord-49dda0c3547f4bd39fd08108d7e549aa

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08344135B2