tert-Butanol → tert-butyl 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorophenylcarbamate

HRID 83894ノート

反応式

HRID 83894 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:35]=[CH:34][C:33]([F:36])=[CH:32][CH:31]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:20])[CH3:19])=[CH:16][N:17]=1)C(O)=O.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:45])C=CC=CC=1.CC[N:57]([CH:61](C)C)C(C)C.[CH3:64][C:65]([OH:68])([CH3:67])[CH3:66]>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[C:4]([NH:57][C:61](=[O:45])[O:68][C:65]([CH3:67])([CH3:66])[CH3:64])[CH:8]=[C:9]([F:37])[C:10]=1[CH2:11][S:12][C:13]1[N:14]([C:30]2[CH:31]=[CH:32][C:33]([F:36])=[CH:34][CH:35]=2)[C:15]([C:18]([C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([O:28][CH3:29])[CH:22]=2)([CH3:19])[CH3:20])=[CH:16][N:17]=1

参加物

7

反応物 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 667398303-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluoro-phenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid

生成物 1

HCID 66741137tert-butyl 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorophenylcarbamate

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

To a suspension of 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorobenzoic acid (540 mg) in a mixture of toluene (5 mL) and t-BuOH (1.5 mL) cooled to 0° C. was added diphenyl phosphoryl azide (DPPA) (302 mg, 1.1 eq) followed by DIPEA (1.3 eq, 0.23 mL). During addition of base, white slurry became clear solution. Reaction mixture was heated at 80° C. overnight. LC-MS showed complete conversion. After cooling to ambient temperature, the reaction mixture was diluted with EtOAc and washed with satd NaHCO3. The organic layer was dried, concentrated and purified by chromatography (silica, EtOAc/Hex, 10-60%) to yield tert-butyl 3-chloro-4-((5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-ylthio)methyl)-5-fluorophenylcarbamate (230 mg). MS (EI) m/z 634 (MH+).

後処理

  1. additionDuring addition of base, white slurry
  2. customReaction mixture
  3. temperaturewas heated at 80° C. overnight
  4. temperatureAfter cooling to ambient temperature
  5. washwashed with satd NaHCO3
  6. customThe organic layer was dried
  7. concentrationconcentrated
  8. custompurified by chromatography (silica, EtOAc/Hex, 10-60%)

出典と根拠

ORDレコード
ord-e725f6837984407bb749538b24163c0f
出典データセット
uspto-grants-2014_09
特許番号
US08846739B2

反応ノート

読み込み中…