Methyl 2-ethylbutyrate → 2-(4-Benzyloxy-3-methyl-phenyl)-2-ethyl-butyric acid methyl ester

HRID 1442680

Reaktionsgleichung

Reaktionsgleichung von HRID 1442680
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12](I)=[CH:11][C:10]=1[CH3:16])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:27][O:28][C:29](=[O:35])[CH:30]([CH2:33][CH3:34])[CH2:31][CH3:32]>C1(C)C=CC=CC=1.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[CH3:27][O:28][C:29](=[O:35])[C:30]([C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[C:10]([CH3:16])[CH:11]=1)([CH2:33][CH3:34])[CH2:31][CH3:32]

Komponenten

8

Edukt 3

HCID 69951Methyl 2-ethylbutyrateHCID 2733832Lithium HexamethyldisilazideHCID 589043791-(Benzyloxy)-4-iodo-2-methylbenzene

Produkt 1

HCID 591667152-(4-Benzyloxy-3-methyl-phenyl)-2-ethyl-butyric acid methyl esterAusbeute 44,9 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 83681Tris(1,1-dimethylethyl)phosphineKatalysatorHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumKatalysatorHCID 1140TolueneLösungsmittel3×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a mixture of 1-benzyloxy-4-iodo-2-methyl-benzene (494 mmoles; 160 g) and lithium bis(trimethylsilyl)amide (1.20 moles; 200 g) in 250 ml of toluene at 0-5° C. is added a solution of 2-ethyl-butyric acid methyl ester (988 mmoles; 129 g, Synthesis, 1985 (3), 320) in 250 ml of toluene over 30 m, causing the reaction to exotherm to 18 C. The cloudy yellow solution is allowed to warm to RT and stir for 20 m. Tri-tert-butylphosphine (4.94 mmoles; 1.30 mL; 1.00 g) in 200 ml of toluene and bis(dibenzylideneacetone)palladium (7.90 mmoles; 4.54 g) are added sequentially, and the dark mixture is stirred at ambient temperature for 62 h. The mixture is diluted with 1 L of EtOAc, filtered through a bed of Hyflo, and rinsed with another 1 L of EtOAc. The filtrate is concentrated. The dark orange oil (˜200 g) is purified by flash chromatography (10% EtOAc/hexanes, 1 kg of silica) to give the title compound as a light orange oil (72.4 g). The mixed fractions are combined and re-subjected to the same chromatography conditions to give the another batch of title compound as a yellow oil (50.6 g). 1H NMR (CDCl3) δ 7.40 (m, 5H), 7.02 (m, 2H), 6.83 (d, J=9.2 Hz, 1H), 5.06 (s, 3H), 3.64 (s, 3H), 2.27 (s, 3H), 2.02 (m, 4H), 0.73 (t, J=7.4 Hz, 6H).

Aufarbeitung

  1. customthe reaction
  2. stirringthe dark mixture is stirred at ambient temperature for 62 h
  3. filtrationfiltered through a bed of Hyflo
  4. washrinsed with another 1 L of EtOAc
  5. concentrationThe filtrate is concentrated
  6. customThe dark orange oil (˜200 g) is purified by flash chromatography (10% EtOAc/hexanes, 1 kg of silica)

Quellen und Nachweise

ORD-Eintrag
ord-a71fa3ca97d642c0b2f10c597dea7288
Quelldatensatz
uspto-grants-2010_02
Patentnummer
US07659296B2

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