Dichloromethane → Methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate

HRID 2373713ノート

反応式

HRID 2373713 の反応式
Br[C:2]1[C:3]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:14])=[CH:9][CH:8]=2)[S:5][CH:6]=1.[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1B(O)O.C([O-])([O-])=O.[K+].[K+].ClCCl>O1CCOCC1.O.CCOC(C)=O.CCCCCC>[Cl:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[C:2]1[C:3]([CH2:21][C:22]([O:24][CH3:25])=[O:23])=[C:4]([C:7]2[CH:12]=[CH:11][C:10]([C:13]([NH:15][CH:16]([CH2:19][CH3:20])[CH2:17][CH3:18])=[O:14])=[CH:9][CH:8]=2)[S:5][CH:6]=1

参加物

9

反応物 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 27343222-Chlorophenylboronic acidHCID 86607182Methyl [4-bromo-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate

生成物 1

HCID 86607183Methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate収率 74.1%

試薬・触媒・溶媒 4

HCID 962Water溶媒HCID 8058Hexane溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒2 回

実験手順

Methyl [4-bromo-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.200 g, 0.5 mmol) was dissolved in dioxane (3 mL) and 2-chlorophenylboronic acid (0.156 g, 1.0 mmol). K2CO3 (0.207 g, 1.5 mmol) was dissolved in H2O (0.2 mL) and added to the dioxane. The solution was degassed by bubbling argon through the mixture for five minutes. {1,1′-Bis(diphenylphosphino)-ferrocene}dichloropalladium(II) complex with dichloromethane (1:1) (0.012 g, 0.015 mmol) was added and the mixture heated under argon to 70° C. for 3 hours (followed by TLC 15:1 hexane:EtOAc). The solvents were removed and the mixture partitioned between EtOAc and H2O. The EtOAc layer was dried (MgSO4) and absorbed onto silica gel. The product was purified by flash chromatography (20:1 hexane:EtOAc) to yield methyl [4-(2-chlorophenyl)-2-(4-{[(1-ethylpropyl)amino]carbonyl}phenyl)thien-3-yl]acetate (0.169 g) as a white solid. mp 57-59° C.; 1H NMR (500 MHz, DMSO-d6) δ: 0.87 (t, 6H, J=7.3 Hz), 1.50 (m, 2H), 1.55 (m, 2H), 3.35 (s, 3H), 3.53 (s, 2H), 3.75 (m, 1H), 7.31 (d, 1H, J=7.2 Hz), 7.43 (m, 3H), 7.59 (m, 3H), 7.96 (d, 2H, J=8.4 Hz), 8.12 (d, 1H, J=8.7 Hz). MS (ES) m/z456.1 ([M+H]+). MS (ES) m/z488.1 ([M+CH3OH+H]+). MS (ES) m/z 911.2 ([2M+H]+). Anal. Calcd for C25H26ClNO3S: C, 65.85; H, 5.75; N, 3.07. Found: C, 65.92; H, 5.96; N, 3.27.

後処理

  1. customThe solution was degassed
  2. customby bubbling argon through the mixture for five minutes
  3. customThe solvents were removed
  4. customthe mixture partitioned between EtOAc and H2O
  5. dry with materialThe EtOAc layer was dried (MgSO4)
  6. customabsorbed onto silica gel
  7. customThe product was purified by flash chromatography (20:1 hexane:EtOAc)

出典と根拠

ORDレコード
ord-59ed782f7af540ab9671fa07a0656e0f
出典データセット
uspto-grants-2008_12
特許番号
US07459567B2

反応ノート

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