Imidazole → (S)-tert-butyl 1-(tert-butyldimethylsilyloxy)-3-cyclopropylbut-3-en-2-ylcarbamate

HRID 627244ノート

反応式

HRID 627244 の反応式
[CH:1]1([C:4]([C@H:6]2[CH2:10][O:9]C(C)(C)[N:7]2[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[CH2:5])[CH2:3][CH2:2]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(N(CC)CC)C.C(OC(OC(C)(C)C)=O)(OC(C)(C)C)=O.N1C=CN=C1.[Si:59](Cl)([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60]>CO.CN(C)C1C=CN=CC=1>[Si:59]([O:9][CH2:10][C@@H:6]([NH:7][C:13](=[O:14])[O:15][C:16]([CH3:17])([CH3:18])[CH3:19])[C:4]([CH:1]1[CH2:2][CH2:3]1)=[CH2:5])([C:62]([CH3:65])([CH3:64])[CH3:63])([CH3:61])[CH3:60]

参加物

9

反応物 6

HCID 795ImidazoleHCID 8471TriethylamineHCID 28928tert-Butyldimethylsilyl chlorideHCID 90495Di-tert-butyl dicarbonateHCID 521998p-Toluenesulfonic acid monohydrate2 回HCID 89851406(S)-tert-butyl 4-(1-cyclopropylvinyl)-2,2-dimethyloxazolidine-3-carboxylate2 回

生成物 1

HCID 89852294(S)-tert-butyl 1-(tert-butyldimethylsilyloxy)-3-cyclopropylbut-3-en-2-ylcarbamate収率 64.2%

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 887Methanol溶媒

反応条件

温度
80 °C

実験手順

To a solution of (S)-tert-butyl 4-(1-cyclopropylvinyl)-2,2-dimethyloxazolidine-3-carboxylate (Intermediate 232, 8.25 g, 30.86 mmol) in methanol (100 mL) at room temperature was added p-toluenesulfonic acid monohydrate (1.174 g, 6.17 mmol). The reaction mixture was heated to 80° C. overnight. Another 0.2 eq of p-toluenesulfonic acid monohydrate was added. Continue heating at 80° C. for 2 hours. The reaction mixture was cooled to room temperature. Triethylamine (4.29 mL, 30.86 mmol) and di-tert-butyl dicarbonate (3.37 g, 15.43 mmol) were added. The reaction mixture was stirred over the weekend then concentrated. The residue was dissolved in ethyl acetate and washed once with saturated sodium bicarbonate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated. The resulting oil was dissolved in DCM (100 mL). Imidazole (2.73 g, 40.11 mmol), 4-dimethylaminopyridine (0.754 g, 6.17 mmol) and tert-butyldimethylsilyl chloride (4.65 g, 30.86 mmol) were added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was filtered to remove solids and washed with brine twice. The organic layer was dried over magnesium sulfate, filtered and concentrated. Silica gel chromatography (0%-10% ethyl acetate/hexanes) afforded the title compound as a colorless oil (6.77 g, 64%).

後処理

  1. temperatureContinue heating at 80° C. for 2 hours
  2. temperatureThe reaction mixture was cooled to room temperature
  3. concentrationthen concentrated
  4. dissolutionThe residue was dissolved in ethyl acetate
  5. washwashed once with saturated sodium bicarbonate
  6. dry with materialThe combined organic extracts were dried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionThe resulting oil was dissolved in DCM (100 mL)
  10. stirringthe reaction mixture was stirred overnight at room temperature
  11. filtrationThe reaction mixture was filtered
  12. customto remove solids
  13. washwashed with brine twice
  14. dry with materialThe organic layer was dried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated

出典と根拠

ORDレコード
ord-9ecad479b36e4d43a33545a9af50a967
出典データセット
uspto-grants-2016_04
特許番号
US09309245B2

反応ノート

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