Isobutyl chloroformate → (2-Amino-4-methoxyphenyl)methanol

Temperatur

-15 °C

To a solution of commercially available 4-methoxy-2-nitrobenzoic acid (4.0 g, 20.66 mmol) in tetrahydrofuran (20 mL) at −15° C. under nitrogen was added N-methylmorphorine (2.2 ml, 20 mmol) followed by isobutyl chloroformate (2.6 mL, 20 mmol) in portions. After 5 min, the reaction was filtered and the solid was rinsed with tetrahydrofuran (20 mL). The filtrate was cooled to −15° C. and a solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate. The reaction was stirred for 5 min. The reaction mixture was partitioned between water and dichloromethane, and extracted aqueous layer with dichloromethane (3×100 mL). The combined organic layers were washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was redissolved in tetrahydrofuran (35 mL) and added palladium (10% on carbon, 400 mg) and stirred under hydrogen gas for 18 hours. The reaction mixture was then filtered through celite and concentrated under reduced pressure. The residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2) gave 744 mg (24% yield) of product as a yellow solid.

1. filtrationthe reaction was filtered
2. washthe solid was rinsed with tetrahydrofuran (20 mL)
3. additiona solution of sodium borohydride in water (3 M, 10 mL) was added to the filtrate
4. customThe reaction mixture was partitioned between water and dichloromethane
5. extractionextracted aqueous layer with dichloromethane (3×100 mL)
6. washThe combined organic layers were washed with brine
7. dry with materialdried over magnesium sulfate
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was redissolved in tetrahydrofuran (35 mL)
10. additionadded palladium (10% on carbon, 400 mg)
11. stirringstirred under hydrogen gas for 18 hours
12. filtrationThe reaction mixture was then filtered through celite and
13. concentrationconcentrated under reduced pressure
14. customThe residue was chromatographed on silica gel with hexanes/ethyl acetate (3:2)

ORD-Eintrag

ord-f5f7cd48bba249f2ba299b450e95a6f6

Quelldatensatz

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08124602B2