Triethylamine → {(1S,2S)-1-[5-(2-fluoro-4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester

HRID 561982ノート

反応式

HRID 561982 の反応式
[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]([C:17]1[NH:18][C:19]([C:22]2[CH:27]=[CH:26][C:25](I)=[CH:24][C:23]=2[F:29])=[CH:20][N:21]=1)[C@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:38][Si:39]([C:42]#[CH:43])([CH3:41])[CH3:40].C(OCC)(=O)C>CN(C)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>[C:1]([O:5][C:6](=[O:30])[NH:7][C@H:8]([C:17]1[NH:18][C:19]([C:22]2[CH:27]=[CH:26][C:25]([C:43]#[C:42][Si:39]([CH3:41])([CH3:40])[CH3:38])=[CH:24][C:23]=2[F:29])=[CH:20][N:21]=1)[C@H:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:10])([CH3:4])([CH3:3])[CH3:2]

参加物

8

反応物 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 66111TrimethylsilylacetyleneHCID 67001487{(1S,2S)-1-[5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester

生成物 1

HCID 67001332{(1S,2S)-1-[5-(2-fluoro-4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester収率 96.1%

試薬・触媒・溶媒 3

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

実験手順

A solution of {(1S,2S)-1-[5-(2-fluoro-4-iodo-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester (286 mg, 0.55 mmol) (prepared in step 30-E), copper (I) iodide (10.50 mg, 0.055 mmol) and dichlorobis(triphenylphosphine)palladium(II) (39 mg, 0.055 mmol) in N,N-dimethylformamide (5 mL) was degassed with dry nitrogen with stirring for 5 minutes. Triethylamine (229 μL, 1.65 mmol) and trimethylsilylacetylene (233 μL, 1.65 mmol) were added and the resulting solution was stirred for 24 hours at room temperature. The reaction was poured into ethyl acetate (25 mL) and washed with water (2×10 mL). The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by chromatography over silica gel gradient eluted between 10 and 50% v/v ethyl acetate in hexanes to give {(1S,2S)-1-[5-(2-fluoro-4-trimethylsilanylethynyl-phenyl)-1H-imidazol-2-yl]-2-phenyl-propyl}-carbamic acid tert-butyl ester (260 mg, 96%). HR-MS: calcd for C28H34FN3O2Si [M+H+] 492.2477. Found 492.2475.

後処理

  1. stirringthe resulting solution was stirred for 24 hours at room temperature
  2. washwashed with water (2×10 mL)
  3. washThe organic layer was washed with brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by chromatography over silica gel gradient
  8. washeluted between 10 and 50% v/v ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-242a0a85998645ef9b589d672b70a1e7
出典データセット
uspto-grants-2011_11
特許番号
US08063085B2

反応ノート

読み込み中…