Trimethylsilyl triflate → HCID 86710545, compound

HRID 1027153Notes

Reaction equation

HRID 1027153 reaction equation
[Si]([O:8][C@@H:9]([CH3:21])/[CH:10]=[N:11]/[CH2:12][C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)(C(C)(C)C)(C)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.C([Si](C)(C)[O:39][C:40]([CH:42]=[C:43]([CH3:45])[CH3:44])=[CH2:41])(C)(C)C.C([O-])(O)=O.[Na+].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>ClCCl>[OH:8][C@H:9]([C@H:10]1[N:11]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[C:43]([CH3:45])([CH3:44])[CH2:42][C:40](=[O:39])[CH2:41]1)[CH3:21].[OH:8][C@H:9]([C@@H:10]1[N:11]([CH2:12][C:13]2[CH:14]=[CH:15][C:16]([O:19][CH3:20])=[CH:17][CH:18]=2)[C:43]([CH3:45])([CH3:44])[CH2:42][C:40](=[O:39])[CH2:41]1)[CH3:21]

Participants

8

Reactant 5

HCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 10899947Tert-butyldimethyl(4-methylpenta-1,3-dien-2-yloxy)silaneHCID 178491099HCID 178491099, compound

Product 2

HCID 86710545HCID 86710545, compoundYield 41%HCID 86710546(R)-6-((S)-1-hydroxyethyl)-1-(4-methoxybenzyl)-2,2-dimethylpiperidin-4-oneYield 31%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of (S,E)-N-(2-(tert-butyldimethylsilyloxy)propylidene)-1-(4-methoxyphenyl)methanamine (3.38 g, 11 mmol) in dichloromethane (90 mL) was added TMSOTf (2.2 mL, 12.1 mmol) and tert-butyldimethyl(4-methylpenta-1,3-dien-2-yloxy)silane (9.35 g, 44 mmol) at 0° C. After stirring for 2 days at 0° C., the reaction mixture was poured into aq. NaHCO3 solution (100 mL), followed by extraction with dichloromethane (100 mL×2). The combined organic layers were dried over MgSO4, and the solvent was evaporated. The residue was dissolved in THF (60 mL) and then 41.8 mL of TBAF (1 M in THF, 41.8 mmol) was added to the solution. The mixture was stirred for 12 h, quenched with water (100 mL), extracted with dichloromethane (100 mL×2), and the combined extracts were dried over Na2SO4. After the solvent was concentrated in vacuo, the product was purified by column chromatography (Et2O/Heptane) to give 1.3 g (41%) of (S)-6-((S)-1-hydroxyethyl)-1-(4-methoxybenzyl)-2,2-dimethylpiperidin-4-one and 1.0 g (31%) of (R)-6-((S)-1-hydroxyethyl)-1-(4-methoxybenzyl)-2,2-dimethylpiperidin-4-one.

Workup

  1. extractionfollowed by extraction with dichloromethane (100 mL×2)
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. customthe solvent was evaporated
  4. dissolutionThe residue was dissolved in THF (60 mL)
  5. stirringThe mixture was stirred for 12 h
  6. customquenched with water (100 mL)
  7. extractionextracted with dichloromethane (100 mL×2)
  8. dry with materialthe combined extracts were dried over Na2SO4
  9. concentrationAfter the solvent was concentrated in vacuo
  10. customthe product was purified by column chromatography (Et2O/Heptane)

Sources & evidence

ORD record
ord-fddfda52336c47c5a3e48aaa0b1c572e
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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