Diisopropylamine → 4-[2-Hydroxy-1,1-dimethyl-3-(4-pyrimidinyl)-2-propenyloxy]benzonitrile

温度

-78 °C

The 6-[5-cyano-2-hydroxy-α-(2-methylpropenyl)benzyl]pyrimidine 1-oxide used as the starting material was prepared as follows: (A) 10 ml of a 1.2M solution of butyllithium in n-hexane were added to a solution of 1.68 ml of diisopropylamine in 50 ml of tetrahydrofuran while stirring at -78° C. under a nitrogen atmosphere. The solution was stirred for a further 15 minutes and a solution of 4-methylpyrimidine in 20 ml of tetrahydrofuran was then added. The solution was allowed to warm to 20° C. and was stirred for 2 hours. The solution was then cooled to -78° C, 2.33 g of ethyl 2-(4-cyanophenoxy)-2-methylpropionate in 30 ml of tetrahydrofuran were added and the mixture was allowed to warm to 20° C. and was stirred for 16 hours. The mixture was then partitioned between ethyl acetate and water. The organic phase was washed with sodium chloride solution and evaporated. The residue was chromatographed on silica gel using ethyl acetate for the elution to give 0.69 g of 4-[2- hydroxy-1,1-dimethyl-3-(4-pyrimidinyl)-2-propenyloxy]benzonitrile in the form of a yellow solid of melting point 115°-117° C. (from ethyl acetate/n-hexane). (B) 0.013 mg of sodium borohydride was added to a solution of 0.098 mg of 4-[2-hydroxy-1,1-dimethyl-3-(4-pyrimidinyl)-2-propenyloxy]benzonitrile in 3 ml of ethanol and the solution was stirred at 20° C. for 16 hours. The solvent was removed by evaporation and the residue was partitioned between ethyl acetate and water. The organic phase was evaporated and the residue was chromatographed on silica gel using ethyl acetate for the elution. There was obtained 0.073 g of 4-[2-hydroxy-1,1-dimethyl-3-(4-pyrimidinyl)propoxy]benzonitrile in the form of a white solid of melting point 96°- 98° C. (C) 3.77 g of m-chloroperbenzoic acid were added to a solution of 4.78 g of 4-[2-hydroxy-1,1-dimethyl-3-(4-pyrimidinyl)propoxy]benzonitrile in 75 ml of dichloromethane and the mixture was stirred at 20° C. for 16 hours. A further 0.38 g of m-chloroperbenzoic acid was added and the mixture was stirred at 20° C. for 24 hours. The mixture was then washed in succession with water and sodium chloride solution. The organic solution was evaporated and the residue was chromatographed on silica gel using diethyl ether/methanol (9:1) for the elution to give 0.98 g of 6-[3-(4-cyanophenoxy)-2-hydroxy-3-methylbutyl]pyrimidine 1-oxide in the form of a white solid of melting point 105°-107.5° C. (from ethyl acetate). (D) 0.23 g of methanesulphonyl chloride was added to a solution of 0.59 g of 6-[3-(4-cyanophenoxy)-2-hydroxy-3-methylbutyl]pyrimidine 1-oxide and 0.2 g of triethylamine in 10 ml of dichloromethane. The mixture was stirred at 20° C. for 2 hours and then a further 0.46 g of methanesulphonyl chloride and 0.4 g of triethylamine were added. After 2 hours a further 0.6 g of triethylamine was added and the mixture was stirred for 1.5 hours. The mixture was then washed with water and evaporated. The residue was chromatographed on silica gel using ethyl acetate for the elution to give 0.25 g of (E)-6-[3-(4-cyanophenoxy)-3-methyl-1-butenyl]pyrimidine 1-oxide in the form of a pale yellow solid of melting point 101°-102° C. (E) 0.24 g of (E)-6-[3-(4-cyanophenoxy)-3-methyl-1-butenyl]pyrimidine 1-oxide in 30 ml of toluene was heated to reflux for 16 hours. The solvent was then removed by evaporation and the residue was chromatographed on silica gel using ethyl acetate for the elution. There was obtained 0.08 g of 6-[5-cyano-2-hydroxy-α-(2-methylpropenyl)benzyl]pyrimidine 1-oxide in the form of a white solid of melting point 190°-192° C. (from ethyl acetate).

1. customwas prepared
2. stirringThe solution was stirred for a further 15 minutes
3. temperatureto warm to 20° C.
4. stirringwas stirred for 2 hours
5. temperatureThe solution was then cooled to -78° C
6. temperatureto warm to 20° C.
7. stirringwas stirred for 16 hours
8. customThe mixture was then partitioned between ethyl acetate and water
9. washThe organic phase was washed with sodium chloride solution
10. customevaporated
11. customThe residue was chromatographed on silica gel
12. washfor the elution

ORDレコード

ord-1095d85d6378485f91fee4cb9f048acc

出典データセット

uspto-grants-1992_06

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05118694