Hydrochloric Acid → HCID 13033428, compound

Temperature

0 °C

To a solution of diisopropylamine (19.74 ml, 140.8 mmol) in 100 ml of anhydrous THF was added dropwise n-butyl lithium (1.44N, 97.8 ml, 140.8 mmol) at 0° C. under argon atmosphere. The mixture was stirred at 0° C. for 1 hour and a half, and then 3-cyclohexylpropionic acid (10.00 g, 64.0 mmol) was added dropwise. After the mixture was stirred at 0° C. for 10 minutes, HMPA (24.5 ml, 140.8 mmol) was added dropwise and the mixture was stirred for 20 minutes. Methyl iodide (8.4 ml, 134.4 mmol) was further added dropwise at 0° C. and the mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with an aqueous saturated solution of ammonium chloride, and acidified to pH 2 with concentrated hydrochloric acid. The mixture was extracted with ethyl acetate (50 ml×4), and then, the combined ethyl acetate layers were washed with water (50 ml) and brine (50 ml), dried over anhydrous sodium sulfate, and concentrated. The residue was distilled to give a crude product of 3-cyclohexyl-2-methylpropionic acid (b.p. 90.5°-101° C./0.2 mmHg, 11.8556 g). To a solution of this crude product in 100 ml of ether was added dropwise 110 ml of a solution of diazomethane in ether at 0° C. After concentration, the residue was separated and purified through column chromatography (silica gel, ether), to give a pure product of methyl 3-cyclohexyl-2-methylpropionate (10.8672 g, 59.0 mmol, 92.2%). This compound was assigned the structure by the following data:

1. stirringAfter the mixture was stirred at 0° C. for 10 minutes
2. stirringthe mixture was stirred for 20 minutes
3. stirringthe mixture was stirred at room temperature for 2 hours
4. extractionThe mixture was extracted with ethyl acetate (50 ml×4)
5. washthe combined ethyl acetate layers were washed with water (50 ml) and brine (50 ml)
6. dry with materialdried over anhydrous sodium sulfate
7. concentrationconcentrated
8. distillationThe residue was distilled

ORD record

ord-51ea45561af84386afcce372f2c64df5

Source dataset

uspto-grants-1988_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04775692