반응 #70188

반응 방정식

potassium hydroxide

2-methylbenzoic acid methyl ester

Diazomethane

N-Nitroso-N-methylurea

diazomethane

diazomethane

4-Isopropenyl-2-methyl-benzoic acid methyl ester

diazomethane

methyl styrene

→

2-Methyl-4-(1-methyl-cyclopropyl)-benzoic acid methyl ester

수율 87.1%

용매

diethyl ether

diethyl ether

반응 조건

후처리

1. 1
   기타was separated
2. 2
   workup.ADDITIONCyclopropanation by adding diazomethane solution to methyl styrene
3. 3
   온도cooled to 0° C
4. 4
   workup.ADDITIONwas added dropwise
5. 5
   여과The reaction mixture was filtered over cellulose
6. 6
   세척washed with diethyl ether
7. 7
   농축concentrated
8. 8
   기타The residue (brown liquid) was purified by 40 g silica gel chromatography (gradient elution 0-100% ethyl acetate in hexane for 15 min) 2.9 g of a crude light yellow liquid
9. 9
   기타was obtained
10. 10
    기타The crude residue was purified again by 110 g flash chromatography (gradient elution 0-20% EtOAc in Hex for 30 min)

실험 절차

Formation of Diazomethane: N-Nitroso-N-methylurea (9.1 g, 61.8 mmol) was added under stirring in portions to a two phase mixture of 50 ml potassium hydroxide solution (23.9 g in 50 ml water) and 50 ml diethyl ether at 0° C. The color of the organic phase changed from colorless to yellow. The two phase mixture was vigorously stirred for 40 min at 0° C. The organic layer that contains diazomethane was separated. Cyclopropanation by adding diazomethane solution to methyl styrene: 4-Isopropenyl-2-methyl-benzoic acid methyl ester (2.94 g, 15.45 mmol) was dissolved in 15 ml diethyl ether and cooled to 0° C. Palladium (II) acetate (0.173 g, 0.773 mmol) was added. The yellow organic phase (containing diazomethane) was added dropwise. In total 20 ml of the organic phase (approximately 4 eq. of diazomethane) was added until the reaction was done. You observe releasing nitrogen by adding diazomethane to the methyl styrene intermediate. The reaction mixture was filtered over cellulose; washed with diethyl ether; concentrated; The residue (brown liquid) was purified by 40 g silica gel chromatography (gradient elution 0-100% ethyl acetate in hexane for 15 min) 2.9 g of a crude light yellow liquid was obtained. NMR shows 8% 2-methylbenzoic acid methyl ester. The crude residue was purified again by 110 g flash chromatography (gradient elution 0-20% EtOAc in Hex for 30 min) to give 2-Methyl-4-(1-methyl-cyclopropyl)-benzoic acid methyl ester (2.75 g, 13.46 mmol) MS (ESI) 268.9 (M+Na++ACN)

출처