Diiodomethane → 9-Chloro-6-[1-(cyclopropyloxy)-2,2,2-trifluoroethyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole

HRID 1399203ノート

反応式

HRID 1399203 の反応式
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([OH:28])[C:24]([F:27])([F:26])[F:25])=[CH:4][CH:3]=1.C(OC=C)(=O)C.C(=O)([O-])[O-].[Na+].[Na+].C([Zn]CC)C.CCC[CH2:49][CH2:50][CH3:51].ICI>ClC1C=CC=CC=1Cl.C(OCC)(=O)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]3[N:11]([C:15]4[CH:20]=[CH:19][C:18]([Cl:21])=[CH:17][C:16]=4[Cl:22])[CH2:12][CH2:13][CH2:14][N:7]3[C:6]=2[C:5]([CH:23]([O:28][CH:49]2[CH2:50][CH2:51]2)[C:24]([F:25])([F:26])[F:27])=[CH:4][CH:3]=1

参加物

9

反応物 6

HCID 6346DiiodomethaneHCID 7904Vinyl AcetateHCID 8058HexaneHCID 10340Sodium CarbonateHCID 577861691-[9-Chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanolHCID 178418750HCID 178418750、化合物

生成物 1

HCID 577857809-Chloro-6-[1-(cyclopropyloxy)-2,2,2-trifluoroethyl]-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazole収率 37%

試薬・触媒・溶媒 2

HCID 72391,2-Dichlorobenzene溶媒HCID 8857Ethyl Acetate溶媒

実験手順

A suspension of 1-[9-chloro-1-(2,4-dichlorophenyl)-1,2,3,4-tetrahydropyrimido[1,2-a]benzimidazol-6-yl]-2,2,2-trifluoroethanol (135 mg, 0.300 mmol), vinyl acetate (277 μL, 3.00 mmol), di-μ-chlorobis[(η-cycloocta-1,5-diene)iridium (I)] (50.4 mg, 0.0750 mmol) and sodium carbonate (19.1, mg, 0.180 mmol) in o-dichlorobenzene (3.0 mL) was stirred for 27 h at 100° C. The reaction mixture was purified by flash column chromatography on silica gel eluting with a 25% ethyl acetate/n-hexane. The obtained compound was dissolved in dichloromethane (1.6 mL). A solution of diethyl zinc in hexane (1.0 M, 818 μL, 0.818 mmol) and diiodomethane (132 μL, 1.64 mmol) was added at 0° C. After being stirred for 4 h at room temperature, the reaction mixture was diluted with ethyl acetate, quenched with aqueous ammonium chloride, washed with water and brine, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on NH silica gel eluting with a 0-12% ethyl acetate/n-hexane gradient mixture to give the title compound as a colorless solid (62.9 mg, 0.110 mmol, 37%). Analytically pure material was obtained by recrystallization from ethyl acetate/hexane.

後処理

  1. customThe reaction mixture was purified by flash column chromatography on silica gel eluting with a 25% ethyl acetate/n-hexane
  2. dissolutionThe obtained compound was dissolved in dichloromethane (1.6 mL)
  3. customquenched with aqueous ammonium chloride
  4. washwashed with water and brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on NH silica gel eluting with a 0-12% ethyl acetate/n-hexane gradient mixture

出典と根拠

ORDレコード
ord-5d1dec75a9874d13a474fbb4823f6c63
出典データセット
uspto-grants-2014_12
特許番号
US08901141B2

反応ノート

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