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

HRID 59781

Reaction equation

HRID 59781 reaction equation
[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

Participants

7

Reactant 4

HCID 962WaterHCID 3382465Tert-ButanesulfinamideHCID 903901554-(2-Phenyl-chroman-6-yloxy)-cyclohexanoneHCID 178418336HCID 178418336, compound2×

Product 1

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

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

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%).

Workup

  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)

Sources & evidence

ORD record
ord-7e3ddd795d704a859e19c1041b179574
Source dataset
uspto-grants-2016_09
Patent number
US09440941B2

Linked notes

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