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

HRID 1442680

反応式

HRID 1442680 の反応式
[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]

参加物

8

反応物 3

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

生成物 1

HCID 591667152-(4-Benzyloxy-3-methyl-phenyl)-2-ethyl-butyric acid methyl ester収率 44.9%

試薬・触媒・溶媒 4

HCID 83681Tris(1,1-dimethylethyl)phosphine触媒HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladium触媒HCID 1140Toluene溶媒3 回HCID 8857Ethyl Acetate溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-a71fa3ca97d642c0b2f10c597dea7288
出典データセット
uspto-grants-2010_02
特許番号
US07659296B2

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