Sodium Carbonate → 2,5-Dichloro-4-(7-methoxybenzo[b]thiophen-2-yl)-pyrimidine

HRID 1986239ノート

反応式

HRID 1986239 の反応式
C([Li])CCC.[CH3:6][O:7][C:8]1[C:13]2[S:14][CH:15]=[CH:16][C:12]=2[CH:11]=[CH:10][CH:9]=1.B(OC(C)C)(OC(C)C)OC(C)C.C([O-])([O-])=O.[Na+].[Na+].[Cl:36][C:37]1[N:42]=[C:41](Cl)[C:40]([Cl:44])=[CH:39][N:38]=1>C1COCC1.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(Cl)(Cl)Cl.CO>[Cl:36][C:37]1[N:42]=[C:41]([C:15]2[S:14][C:13]3[C:8]([O:7][CH3:6])=[CH:9][CH:10]=[CH:11][C:12]=3[CH:16]=2)[C:40]([Cl:44])=[CH:39][N:38]=1

参加物

11

反応物 5

HCID 10340Sodium CarbonateHCID 21531Triisopropyl borateHCID 2372592,4,5-TrichloropyrimidineHCID 110842177-Methoxybenzo[b]thiopheneHCID 178418339Butyllithium

生成物 1

HCID 866253692,5-Dichloro-4-(7-methoxybenzo[b]thiophen-2-yl)-pyrimidine

試薬・触媒・溶媒 5

HCID 167845palladium(II) acetate触媒HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)触媒HCID 887Methanol溶媒HCID 6212Chloroform溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

n-Butyl lithium (4.19 mL, 1.6 M in hexane) is added dropwise over 1 hour to a stirred solution of 7-methoxy-benzo[b]thiophene (1.00 g, 6.09 mmol) and triisopropyl borate (1.26 g, 6.70 mmol) in anhydrous THF (10 mL) at −78° C. under nitrogen. The resultant mixture is allowed to stir at −78° C. for 30 minutes, then at −20° C. for another 30 minutes. Aqueous Na2CO3 solution (2 M, 6.09 mL) is added to the mixture, followed by the addition of 1,1′-bis(diphenylphosphino)ferrocene (169 mg, 0.304 mmol), palladium(II) acetate (68.3 mg, 0.304 mmol) and 2,4,5-trichloropyrimidine (1.12 g, 6.09 mmol). Then the reaction mixture is heated to reflux for 18 hours. At ambient temperature CH3OH (10 mL) and CHCl3 (90 mL) are added to the mixture. The organic layer is separated, dried over MgSO4, filtered, and concentrated. After chromatographic purification on silica gel eluting with CH3OH in dichloromethane 0-1%, the title compound is obtained as a yellowish solid (40 mg) and 872 mg starting 7-methoxy-benzo[b]thiophene is recovered.

後処理

  1. waitat −20° C. for another 30 minutes
  2. temperatureThen the reaction mixture is heated
  3. temperatureto reflux for 18 hours
  4. customThe organic layer is separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customAfter chromatographic purification on silica gel eluting with CH3OH in dichloromethane 0-1%

出典と根拠

ORDレコード
ord-502d63a8c9184c2ba7e45983fdf60305
出典データセット
uspto-grants-2009_06
特許番号
US07547691B2

反応ノート

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