Reaction #42397

Reaction equation

methanesulfonyl chloride

triethylamine

N-methylbutylamine

3-(methoxycarbonyl)-5-(1,3-oxazol-2-yl)benzoic acid

lithium borohydride

trimethylsilyldiazomethane

hexane

→

title compound

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

Solvents

tetrahydrofuran

ethanol

Conditions

Workup

1. 1
   workup.STIRRINGthe reaction is stirred 1 h
2. 2
   workup.ADDITIONThe solution is poured onto ice containing excess hydrochloric acid
3. 3
   Extractionextracted with ethyl acetate
4. 4
   WashThe organic layer is washed with water, brine
5. 5
   Dryingdried (sodium sulfate)
6. 6
   Filtrationfiltered
7. 7
   Concentrationconcentrated under reduced pressure
8. 8
   workup.DISSOLUTIONThe residue is redissolved in 20% methanol/benzene (50 mL)
9. 9
   workup.STIRRINGThe reaction is stirred 2 h at room temperature
10. 10
    Concentrationconcentrated under reduced pressure
11. 11
    workup.DISSOLUTIONThe residue is redissolved in anhydrous methylene chloride (10 mL)
12. 12
    workup.STIRRINGThe reaction is stirred at 0° C
13. 13
    workup.STIRRINGthe reaction is stirred 16 h at room temperature
14. 14
    ConcentrationThe solution is concentrated under reduced pressure
15. 15
    OtherPurification by flash column chromatography (silica gel, 40-100% ethyl acetate/hexane gradient)

Procedure

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]+.

Source