Methanol → (2R,3R)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-3-(4-(trifluoromethyl)phenyl)aziridine-1-carboxylate

HRID 2075328

反応式

HRID 2075328 の反応式
[H-].[Na+].CS(O[C@@H:8]([CH2:28][O:29][Si:30]([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31])[C@H:9]([NH:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1)(=O)=O.CCOC(C)=O.CO>C1COCC1.CCCCCC>[Si:30]([O:29][CH2:28][C@H:8]1[C@@H:9]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[N:20]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])([C:33]([CH3:36])([CH3:35])[CH3:34])([CH3:32])[CH3:31]

参加物

7

反応物 4

HCID 887MethanolHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 57634118(1R,2R)-1-((tert-Butoxycarbonyl)amino)-3-(tert-butyldimethylsilyloxy)-1-(4-(trifluoromethyl)phenyl)propan-2-yl methanesulfonate

生成物 1

HCID 86613771(2R,3R)-tert-butyl 2-((tert-butyldimethylsilyloxy)methyl)-3-(4-(trifluoromethyl)phenyl)aziridine-1-carboxylate収率 58.8%

試薬・触媒・溶媒 2

HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒

実験手順

To a suspension of 4.0 g sodium hydride (60% dispersion in mineral oil) in 50 mL THF at 0° C. was added a solution (1R,2R)-1-((tert-butoxycarbonyl)amino)-3-(tert-butyldimethylsilyloxy)-1-(4-(trifluoromethyl)phenyl)-propan-2-yl methanesulfonate (13.5 g, 25.6 mmol) in 60 mL THF. The reaction progress was monitored by TLC (20% EtOAc in hexane). When no more starting material could be detected, 4 grams of MeOH was added to the mixture to remove the excess sodium hydride. The solvent was then removed at reduced pressure, and 200 mL of distilled water was added to the residue. The aqueous phase was extracted (3×150 mL) with EtOAc. The combined organic layers were washed with brine and dried over sodium sulfate. The crude product was then chromatographed eluting with 3% EtOAc in hexane. After removing the solvent, the product was obtained as a colorless oil (6.5 g, yield=58%). 1H NMR (400 MHz, CD3OD) o ppm 0.14-0.18 (m, 6 H) 0.95-0.98 (m, 9 H) 1.46 (s, 9 H) 2.78 (q, J=2.80 Hz, 1H) 3.64 (d, J=2.93 Hz, 1H) 4.11 (ddd, J=18.19, 11.93, 2.54 Hz, 2H) 7.48 (d, J=8.22 Hz, 2H) 7.66 (d, J=8.02 Hz, 2H).

後処理

  1. customto remove the excess sodium hydride
  2. customThe solvent was then removed at reduced pressure, and 200 mL of distilled water
  3. additionwas added to the residue
  4. extractionThe aqueous phase was extracted (3×150 mL) with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over sodium sulfate
  7. customThe crude product was then chromatographed
  8. washeluting with 3% EtOAc in hexane
  9. customAfter removing the solvent

出典と根拠

ORDレコード
ord-675c53f1086c448389eee92aba00941e
出典データセット
uspto-grants-2011_04
特許番号
US07919504B2

関連ノート

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