1-Hydroxybenzotriazole → rac-3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-N-[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-N-methyl-propionamide

HRID 220313

反応式

HRID 220313 の反応式
C1([C:7]2[N:8]=[C:9]([CH2:26][CH2:27][C:28]([OH:30])=O)[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)C=CC=CC=1.CCN(C(C)C)C(C)C.[CH:40]1[CH:41]=[CH:42][C:43]2N(O)N=N[C:44]=2[CH:45]=1.[CH3:50][NH:51][CH2:52][CH2:53][C:54]1([OH:68])[CH2:59][CH:58]2[CH2:60][CH2:61][CH:55]1[CH:56]=[C:57]2[C:62]1[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>C1COCC1.C(Cl)Cl.C(Cl)CCl>[C:44]1([C:7]2[N:8]=[C:9]([CH2:26][CH2:27][C:28]([N:51]([CH2:52][CH2:53][C@:54]3([OH:68])[CH2:59][C@H:58]4[CH2:60][CH2:61][C@@H:55]3[CH:56]=[C:57]4[C:62]3[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=3)[CH3:50])=[O:30])[N:10]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:23])[CH3:24])[C:11]=2[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:45]=1

参加物

8

反応物 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 684143723-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-propionic acidHCID 68415512rac-(1R*,2R*,4R*)-2-(2-methylamino-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol

生成物 1

HCID 68414528rac-3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-N-[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-N-methyl-propionamide収率 91.9%

試薬・触媒・溶媒 3

HCID 111,2-Dichloroethane溶媒HCID 6344Dichloromethane溶媒2 回HCID 8028Tetrahydrofuran溶媒

実験手順

145 mg of 3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-propionic acid were dissolved in THF (0.13 mL)/DCM (0.5 mL). 0.160 mL of DIPEA, 50 mg of HOBt and 71 mg of EDC were added sequentially at rt. The reaction mixture was stirred for 5 min then 80 mg of rac-(1R*,2R*,4R*)-2-(2-methylamino-ethyl)-5-phenyl-bicyclo[2.2.2]oct-5-en-2-ol were added at rt. The reaction mixture was stirred on at rt then diluted with DCM and washed with sat.-NaHCO3 and brine. The organic phase was dried over anh. Na2SO4, filtered and concentrated in vacuo. The resulting crude material was purified by CC using EtOAc/MeOH/NEt3 as eluant from 100/0/1 to 95/5/1 to yield 189 mg of rac-3-[4,5-diphenyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-N-[2-((1R*,2R*,4R*)-2-hydroxy-5-phenyl-bicyclo[2.2.2]oct-5-en-2-yl)-ethyl]-N-methyl-propionamide as a yellow oil.

後処理

  1. stirringThe reaction mixture was stirred on at rt
  2. washwashed with sat.-NaHCO3 and brine
  3. dry with materialThe organic phase was dried over anh. Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting crude material was purified by CC

出典と根拠

ORDレコード
ord-0dae70123d2048afbcb8e128730f1905
出典データセット
uspto-grants-2012_06
特許番号
US08202885B2

関連ノート

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