Hexane → Methyl 3-{[butyl(methyl)amino]methyl}-5-(1,3-oxazol-2-yl)benzoate

Temperature

-30 °C

To an ice-cold solution of 3-(methoxycarbonyl)-5-(1,3-oxazol-2-yl)benzoic acid (340 mg, 1.4 mmol) in anhydrous tetrahydrofuran (10 mL) is added lithium borohydride (250 mg, 11 mmol) slowly. The reaction is stirred 30 min, then absolute ethanol (4 mL) is added, and the reaction is stirred 1 h. The solution is poured onto ice containing excess hydrochloric acid and extracted with ethyl acetate. The organic layer is washed with water, brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. The residue is redissolved in 20% methanol/benzene (50 mL), and 2M trimethylsilyldiazomethane in hexane (0.9 mL, 1.8 mmol) is added. The reaction is stirred 2 h at room temperature, then concentrated under reduced pressure. The residue is redissolved in anhydrous methylene chloride (10 mL), cooled to −30° C., then methanesulfonyl chloride (150 μL, 1.9 mmol) and triethylamine (380 μL, 2.7 mmol) are added. The reaction is stirred at 0° C. 15 min, then N-methylbutylamine (480 μL, 4 mmol) is added, and the reaction is stirred 16 h at room temperature. The solution is concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 40-100% ethyl acetate/hexane gradient) provides the title compound in pure form. ESI MS m/z 303.3 [M+H]+.

1. stirringthe reaction is stirred 1 h
2. additionThe solution is poured onto ice containing excess hydrochloric acid
3. extractionextracted with ethyl acetate
4. washThe organic layer is washed with water, brine
5. dry with materialdried (sodium sulfate)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe residue is redissolved in 20% methanol/benzene (50 mL)
9. stirringThe reaction is stirred 2 h at room temperature
10. concentrationconcentrated under reduced pressure
11. dissolutionThe residue is redissolved in anhydrous methylene chloride (10 mL)
12. stirringThe reaction is stirred at 0° C
13. stirringthe reaction is stirred 16 h at room temperature
14. concentrationThe solution is concentrated under reduced pressure
15. customPurification by flash column chromatography (silica gel, 40-100% ethyl acetate/hexane gradient)

ORD record

ord-1f463daa79c14d38a51e33b4e0c9aeb8

Source dataset

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07727997B2