Tetrahydrofuran → (S)-2-hydroxy-N,3-bis(4-methoxyphenyl)-2-methylpropanamide

Temperature

-78 °C

To a 500 mL single-necked round-bottomed flask fitted with a stirring bar, rubber stopper and a nitrogen inlet was added (S)—N-(4-methoxyphenyl)-2-methyloxirane-2-carboxamide (1.00 g, 4.83 mmol) and anhydrous THF (50 mL). The solution was cooled to −78° C. in dry ice-acetone bath. 4-Methoxyphenylmagnesium bromide solution (14.50 mL of 0.5 M THF solution, 7.25 mmol) was added dropwise with stirring at −78° C. The resulted solution was stirred at −78° C. for 30 minutes and then at room temperature for 3 hours. The reaction was quenched by adding 20 mL of saturated NH4Cl solution at 0° C. EtOAc (3×30 mL) was added to extract the solution. The organic layers were separated, washed with brine (20 mL) and dried over anhydrous MgSO4. The solvent was removed under reduced pressure and the residue was purified by flash column chromatography (silica gel, EtOAc/hexanes=1/1 v/v) to give a white solid product, (S)-2-hydroxy-N,3-bis(4-methoxyphenyl)-2-methylpropanamide (6c), 0.60 g, 39.5% yield.

1. customTo a 500 mL single-necked round-bottomed flask fitted with a stirring bar
2. stirringThe resulted solution was stirred at −78° C. for 30 minutes
3. customThe reaction was quenched
4. additionby adding 20 mL of saturated NH4Cl solution at 0° C
5. additionEtOAc (3×30 mL) was added
6. extractionto extract the solution
7. customThe organic layers were separated
8. washwashed with brine (20 mL)
9. dry with materialdried over anhydrous MgSO4
10. customThe solvent was removed under reduced pressure
11. customthe residue was purified by flash column chromatography (silica gel, EtOAc/hexanes=1/1 v/v)

ORD record

ord-ccf154efec204d53a32ed718fc52416b

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158828B2