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

HRID 41910

Reaktionsgleichung

Reaktionsgleichung von HRID 41910
[N+](=C)=[N-].N(N(C)[C:7](N)=O)=O.[OH-].[K+].[CH3:13][O:14][C:15](=[O:26])[C:16]1[CH:21]=[CH:20][C:19]([C:22]([CH3:24])=[CH2:23])=[CH:18][C:17]=1[CH3:25].CC=CC1C=CC=CC=1.COC(=O)C1C=CC=CC=1C>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:13][O:14][C:15](=[O:26])[C:16]1[CH:21]=[CH:20][C:19]([C:22]2([CH3:7])[CH2:24][CH2:23]2)=[CH:18][C:17]=1[CH3:25]

Komponenten

9

Edukt 6

HCID 9550Diazomethane4×HCID 12500beta-MethylstyreneHCID 12699N-Methyl-N-nitrosoureaHCID 14797Potassium HydroxideHCID 33094Methyl o-toluateHCID 592165214-Isopropenyl-2-methyl-benzoic acid methyl ester

Produkt 1

HCID 592165062-Methyl-4-(1-methyl-cyclopropyl)-benzoic acid methyl esterAusbeute 87,1 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 3283Diethyl EtherLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

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)

Aufarbeitung

  1. customwas separated
  2. additionCyclopropanation by adding diazomethane solution to methyl styrene
  3. temperaturecooled to 0° C
  4. additionwas added dropwise
  5. filtrationThe reaction mixture was filtered over cellulose
  6. washwashed with diethyl ether
  7. concentrationconcentrated
  8. customThe 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. customwas obtained
  10. customThe crude residue was purified again by 110 g flash chromatography (gradient elution 0-20% EtOAc in Hex for 30 min)

Quellen und Nachweise

ORD-Eintrag
ord-abf89a8bd8384a3ea2ae8e5eb966b4e7
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08536166B2

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