Diisopropylamine → 6-[2-cyclopentyl-4-(3-fluoro-4-isopropylphenyl)-2-hydroxybut-3-ynyl]-2,2-dimethyl-4H-1,3-dioxin-4-one

HRID 1453036ノート

反応式

HRID 1453036 の反応式
Br[C:2]1[CH:7]=[CH:6][C:5]([CH:8]([CH3:10])[CH3:9])=[C:4]([F:11])[CH:3]=1.[CH:12]1([C:17]([OH:30])([C:28]#[CH:29])[CH2:18][C:19]2[O:24][C:23]([CH3:26])([CH3:25])[O:22][C:21](=[O:27])[CH:20]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1.C(NC(C)C)(C)C>CN(C=O)C.CCOC(C)=O.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH:12]1([C:17]([OH:30])([C:28]#[C:29][C:2]2[CH:7]=[CH:6][C:5]([CH:8]([CH3:10])[CH3:9])=[C:4]([F:11])[CH:3]=2)[CH2:18][C:19]2[O:24][C:23]([CH3:26])([CH3:25])[O:22][C:21](=[O:27])[CH:20]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1

参加物

8

反応物 3

HCID 7912DiisopropylamineHCID 210510924-Bromo-2-fluoro-1-(1-methylethyl)benzeneHCID 224998026-(2-Cyclopentyl-2-hydroxy-but-3-ynyl)-2,2-dimethyl-[1,3]dioxin-4-one

生成物 1

HCID 587625876-[2-cyclopentyl-4-(3-fluoro-4-isopropylphenyl)-2-hydroxybut-3-ynyl]-2,2-dimethyl-4H-1,3-dioxin-4-one収率 89.2%

試薬・触媒・溶媒 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
90 °C

実験手順

4-Bromo-2-fluoro-1-isopropylbenzene (5.0 g, 23.2 mmol), 6-(2-cyclopentyl-2-hydroxybut-3-ynyl)-2,2-dimethyl-4H-1,3-dioxin-4-one (5.56 g, 21.0 mmol) were dissolved in anhydrous DMF (30 mL). To this solution, CuI (120 mg, 0.63 mmol), Pd(PPh3)2Cl2 (0.59 g, 0.84 mmol), and diisopropylamine (60 mL), were added sequentially. The mixture was then heated at 90° C. for 20 min before it was cooled down to 25° C. The reaction was diluted with EtOAc (150 mL) and washed with aqueous NH4Cl, brine, and dried over Na2SO4. The solvent was removed in vacuo and the residue was purified by flash column chromatography (0-40% EtOAc in hexanes) to give the desired product (7.5 g, 81% yield). 1H NMR (CDCl3, 300 MHz) δ: 1.22-1.28 (m, 8H), 1.69-1.74 (m, 10H), 1.80-1.86 (m, 2H), 2.19-2.26 (m, 1H), 2.62-2.70 (m, 2H), 3.18-3.25 (m, 1H), 5.46 (s, 1H), 7.00 (dd, J=10.61, 1.52 Hz, 1H), 7.09-7.11 (m, 1H), 7.18 (t, J=7.71 Hz, 1H).

後処理

  1. temperaturewas cooled down to 25° C
  2. washwashed with aqueous NH4Cl, brine
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed in vacuo
  5. customthe residue was purified by flash column chromatography (0-40% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-27c9ac3b1edb4d968893a45a8db1ab67
出典データセット
uspto-grants-2009_01
特許番号
US07473790B2

反応ノート

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