Dichloromethane → 5-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrile

HRID 1499707ノート

反応式

HRID 1499707 の反応式
Br[C:2]1[C:3]([O:13][CH3:14])=[C:4]([CH:10]([OH:12])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].CC1(C)C(C)(C)OB([C:23]2[CH:24]=[CH:25][C:26]([C:29]#[N:30])=[N:27][CH:28]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].ClCCl>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:9][C:6]1[C:7]([CH3:8])=[C:2]([C:23]2[CH:24]=[CH:25][C:26]([C:29]#[N:30])=[N:27][CH:28]=2)[C:3]([O:13][CH3:14])=[C:4]([CH:10]([OH:12])[CH3:11])[CH:5]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 866668161-(3-Bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol

生成物 1

HCID 866776485-[3-Chloro-5-(1-hydroxyethyl)-6-methoxy-2-methylphenyl]pyridine-2-carbonitrile収率 70%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 6342Acetonitrile溶媒

反応条件

温度
95 °C

実験手順

A mixture of 1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)ethanol (0.15 g, 0.54 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carbonitrile (from Frontier, 0.14 g, 0.59 mmol), sodium carbonate (110 mg, 1.1 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (52 mg, 0.064 mmol) in acetonitrile (4 mL)/water (1 mL) was degassed and then refilled with N2. The reaction was stirred at 95° C. for 2 h, cooled, diluted with ethyl acetate, washed with sat. NaHCO3, water, brine, and then dried over Na2SO4, filtered and concentrated. The crude product was purified by silica gel chromatography, eluting with 0 to 40% EtOAc in hexanes, to give the desired product (114 mg, 70%). LCMS calculated for C16H16ClN2O2 (M+H)+: m/z=303.1; Found: 303.0

後処理

  1. customwas degassed
  2. additionrefilled with N2
  3. temperaturecooled
  4. additiondiluted with ethyl acetate
  5. washwashed with sat. NaHCO3, water, brine
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by silica gel chromatography
  10. washeluting with 0 to 40% EtOAc in hexanes

出典と根拠

ORDレコード
ord-e93d8c2f3c264fea831cb8f7f6af07bf
出典データセット
uspto-grants-2015_12
特許番号
US09199982B2

反応ノート

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