Ammonia → HCID 68828227, compound

Temperature

-78 °C

Under an atmosphere of argon, 2.18 g (12.09 mmol) of 3-(3-methoxyphenyl)propionic acid was put into a three-neck flask, and tetrahydrofuran (20 mL) and tert-butylalcohol (20 mL) were added thereto. After cooling to −78° C., about 150 mL of liquid ammonia was added thereto, and then sodium was added piece by piece. After the reaction was completed, ethanol was added to stop the reaction, and ammonia was removed at room temperature. After sodium dihydrogen phosphate was added thereto to make the reaction mixture acidic, it was extracted with chloroform, dried over magnesium sulfate and filtered, followed by evaporation of the solvent under a reduced pressure. An aqueous solution of acetic acid (acetic acid:distilled water=4:1) was added to the residue and stirred for 45 minutes, and then the solvent was removed under a reduced pressure. To the obtained residue was added 50 mL of ethanol, followed by 8 mL (16 mmol) of 2M trimethylsilyldiazomethane at 0° C. After stirring for 1 hour, the reaction mixture was concentrated under a reduced pressure and then 50 mL of ethanol was added to the obtained residue. Then, 450 mg (11.9 mmol) of sodium borohydride was added thereto at 0° C., and after the reaction was completed, saturated aqueous ammonium chloride solution was added. The resulting mixture was concentrated under a reduced pressure and extracted with ethyl acetate after the saturated aqueous sodium bicarbonate solution was added. The solvent was removed under a reduced pressure, and then the residue was purified by silica gel column chromatography (developing solvent; hexane:ethyl acetate=7:3 to 1:1) to obtain 793 mg (4.3 mmol) of 3-(5-hydroxycyclohexa-1-enyl)propionic acid methyl ester. Its physical property is shown below.

1. customwas removed at room temperature
2. additionAfter sodium dihydrogen phosphate was added
3. extractionit was extracted with chloroform
4. dry with materialdried over magnesium sulfate
5. filtrationfiltered
6. customfollowed by evaporation of the solvent under a reduced pressure
7. additionAn aqueous solution of acetic acid (acetic acid:distilled water=4:1) was added to the residue
8. customthe solvent was removed under a reduced pressure
9. additionTo the obtained residue was added 50 mL of ethanol
10. stirringAfter stirring for 1 hour
11. concentrationthe reaction mixture was concentrated under a reduced pressure
12. addition50 mL of ethanol was added to the obtained residue
13. customat 0° C.
14. concentrationThe resulting mixture was concentrated under a reduced pressure
15. extractionextracted with ethyl acetate after the saturated aqueous sodium bicarbonate solution
16. additionwas added
17. customThe solvent was removed under a reduced pressure
18. customthe residue was purified by silica gel column chromatography (developing solvent; hexane:ethyl acetate=7:3 to 1:1)

ORD record

ord-0cfc68ec8af5428abb6cdc8e74cf36ad

Source dataset

uspto-grants-2009_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07511144B2