Trifluoroacetic acid → 5-{(1R)-4-Cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-N-(4-methoxybenzyl)-1,2,4-oxadiazole-3-carboxamide

HRID 2182915ノート

反応式

HRID 2182915 の反応式
[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([O:22]CC)=O)[N:16]=2)[CH2:11][C:12]([OH:14])=O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:25][O:26][C:27]1[CH:34]=[CH:33][C:30]([CH2:31][NH2:32])=[CH:29][CH:28]=1.CN1CCOCC1.ClC(OCC(C)C)=O.C[Si](C)(C)[O:52][NH2:53].FC(F)(F)C(O)=O>C(O)C.O>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:15]2[O:19][N:18]=[C:17]([C:20]([NH:32][CH2:31][C:30]3[CH:33]=[CH:34][C:27]([O:26][CH3:25])=[CH:28][CH:29]=3)=[O:22])[N:16]=2)[CH2:11][C:12]([NH:53][OH:52])=[O:14])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

参加物

9

反応物 6

HCID 6422Trifluoroacetic acidHCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 754524-MethoxybenzylamineHCID 2734666O-(Trimethylsilyl)hydroxylamineHCID 59909750(3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid

生成物 1

HCID 101607195-{(1R)-4-Cyclohexyl-1-[2-(hydroxyamino)-2-oxoethyl]butyl}-N-(4-methoxybenzyl)-1,2,4-oxadiazole-3-carboxamide収率 11.3%

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒2 回HCID 962Water溶媒

反応条件

温度
80 °C

実験手順

A solution of (3R)-6-cyclohexyl-3-[3-(ethoxycarbonyl)-1,2,4-oxadiazol-5-yl]hexanoic acid (Preparation 4) (500 mg, 1.47 mmol) in ethanol (13 ml) was treated with a solution of 4-methoxybenzylamine (1.00 g, 7.35 mmol) in ethanol (2 ml) and the resulting solution was heated at 80° C. under a nitrogen atmosphere for 10 hours. The solvent was removed under reduced pressure and the residue was dissolved in hydrochloric acid (1M, 10 ml) then extracted with ethyl acetate (×2). The combined organic layers were dried over anhydrous magnesium sulphate, filtered and the solvent removed under reduced pressure. This residue (578 mg) was then dissolved in dichloromethane (15 ml), cooled to 0° C. and treated sequentially with N-methylmorpholine (160 μl, 1.45 mmol) and isobutyl chloroformate (190 μl, 1.47 mmol). This mixture was stirred at 0° C. under a nitrogen atmosphere for 1 hour, then treated with O-(trimethylsilyl)hydroxylamine (195 μl, 1.60 mmol) and stirring continued for 10 minutes at 0° then for 17 hours at room temperature. The mixture was then treated with trifluoroacetic acid:water (5 ml, 9:1) and the solution stirred for 30 minutes. The solvent was removed under reduced pressure and the residue azeotroped from toluene (×2). The residue was purified by HPLCa to afford the title compound as a foam (74 mg).

後処理

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in hydrochloric acid (1M, 10 ml)
  3. extractionthen extracted with ethyl acetate (×2)
  4. dry with materialThe combined organic layers were dried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. dissolutionThis residue (578 mg) was then dissolved in dichloromethane (15 ml)
  8. temperaturecooled to 0° C.
  9. stirringstirring
  10. waitcontinued for 10 minutes at 0°
  11. waitfor 17 hours at room temperature
  12. customThe solvent was removed under reduced pressure
  13. customthe residue azeotroped from toluene (×2)
  14. customThe residue was purified by HPLCa

出典と根拠

ORDレコード
ord-4f3e35a7df7b41dc9da62e62a0755f52
出典データセット
uspto-grants-2005_05
特許番号
US06897306B2

反応ノート

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