Water → 2-Methyl-propane-2-sulfinic acid [1-benzyl-4-(2-phenyl-chroman-6-yloxy)-cyclohexyl]-amide

HRID 59781

反応式

HRID 59781 の反応式
[C:1]1([CH:7]2[CH2:16][CH2:15][C:14]3[C:9](=[CH:10][CH:11]=[C:12]([O:17][CH:18]4[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]4)[CH:13]=3)[O:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:25]([S:29]([NH2:31])=[O:30])([CH3:28])([CH3:27])[CH3:26].[CH2:32]([Mg]Cl)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.O>O1CCCC1.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[CH2:32]([C:21]1([NH:31][S:29]([C:25]([CH3:28])([CH3:27])[CH3:26])=[O:30])[CH2:22][CH2:23][CH:18]([O:17][C:12]2[CH:13]=[C:14]3[C:9](=[CH:10][CH:11]=2)[O:8][CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[CH2:16][CH2:15]3)[CH2:19][CH2:20]1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

参加物

7

反応物 4

HCID 962WaterHCID 3382465Tert-ButanesulfinamideHCID 903901554-(2-Phenyl-chroman-6-yloxy)-cyclohexanoneHCID 178418336HCID 178418336、化合物2 回

生成物 1

HCID 1317370652-Methyl-propane-2-sulfinic acid [1-benzyl-4-(2-phenyl-chroman-6-yloxy)-cyclohexyl]-amide収率 43.5%

試薬・触媒・溶媒 2

HCID 76524Titanium tetraethoxide触媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

実験手順

To a solution of 352 mg of 4-(2-phenyl-chroman-6-yloxy)-cyclohexanone (1.1 mmol) in 10 ml of tetrahydrofuran at room temperature 0.46 ml of titanium(IV) ethoxide (2.18 mmol) and 139 mg of tert-butylsulfinamide (1.15 mmol) were added and the resulting solution heated to reflux for 16 h. The solution was cooled to 0° C. and 1.09 ml of benzylmagnesium chloride (2M in tetrahydrofuran, 2.18 mmol) were added. The mixture was stirred at room temperature for 16 h and additional 1.09 ml of benzylmagnesium chloride solution were added. After additional 16 h of stirring the reaction was stopped by careful addition of water. The suspension was filtered and the filter cake washed with dichloromethane. The aqueous layer was extracted with dichloromethane. The combined organic layers were dried over sodium sulfate and filtered, and the solvent removed by evaporation. The resulting oil was purified by chromatography over silica gel using a heptane/ethyl acetate gradient (0% ethyl acetate to 25% ethyl acetate). 248 mg of 2-methyl-propane-2-sulfinic acid [1-benzyl-4-(2-phenyl-chroman-6-yloxy)-cyclohexyl]-amide were isolated as a mixture of diastereomers (44%).

後処理

  1. temperaturethe resulting solution heated
  2. temperatureto reflux for 16 h
  3. stirringAfter additional 16 h of stirring the reaction
  4. filtrationThe suspension was filtered
  5. washthe filter cake washed with dichloromethane
  6. extractionThe aqueous layer was extracted with dichloromethane
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. filtrationfiltered
  9. customthe solvent removed by evaporation
  10. customThe resulting oil was purified by chromatography over silica gel using a heptane/ethyl acetate gradient (0% ethyl acetate to 25% ethyl acetate)

出典と根拠

ORDレコード
ord-7e3ddd795d704a859e19c1041b179574
出典データセット
uspto-grants-2016_09
特許番号
US09440941B2

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