[Methoxy(tetrahydro-4H-pyran-4-ylidene)methoxy](trimethyl)silane → Methyl 4-[(4-{[(tert-butoxycarbonyl)amino]methyl}piperidin-1-yl)methyl]tetrahydro-2H-pyran-4-carboxylate

HRID 733096Notes

Reaction equation

HRID 733096 reaction equation
C(O[CH2:4][N:5]1[CH2:10][CH2:9][CH:8]([CH2:11][NH:12][C:13](=[O:19])[O:14][C:15]([CH3:18])([CH3:17])[CH3:16])[CH2:7][CH2:6]1)C.[CH3:20][O:21][C:22](=[C:28]1[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1)[O:23][Si](C)(C)C>C(Cl)Cl.FC(F)(F)S(O[Si](C)(C)C)(=O)=O>[C:15]([O:14][C:13]([NH:12][CH2:11][CH:8]1[CH2:7][CH2:6][N:5]([CH2:4][C:28]2([C:22]([O:21][CH3:20])=[O:23])[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[CH2:10][CH2:9]1)=[O:19])([CH3:16])([CH3:17])[CH3:18]

Participants

5

Reactant 2

HCID 24897138[Methoxy(tetrahydro-4H-pyran-4-ylidene)methoxy](trimethyl)silaneHCID 67233964tert-Butyl {[1-(ethoxymethyl)piperidin-4-yl]methyl}carbamate

Product 1

HCID 67233187Methyl 4-[(4-{[(tert-butoxycarbonyl)amino]methyl}piperidin-1-yl)methyl]tetrahydro-2H-pyran-4-carboxylateYield 130.8%

Reagents, catalysts & solvents 2

HCID 65367Trimethylsilyl triflateCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of tert-butyl {[1-(ethoxymethyl)piperidin-4-yl]methyl}carbamate (4 g, 14 mmol, step 1 of Example 8) and [methoxy(tetrahydro-4H-pyran-4-ylidene)methoxy](trimethyl)silane (2.9 g, 13 mmol, step 2 of Example 8) in CH2Cl2 (30 mL) was added dropwise trimethylsilyl trifluoromethanesulfonate (0.24 mL, 1.3 mmol) at 0° C., and the resulting mixture was stirred at room temperature for 12 h. The reaction mixture was quenched with saturated aqueous sodium bicarbonate (150 mL), extracted with CH2Cl2 (30 mL×2), and the combined organic layer was dried over sodium sulfate and filtered. Removal of the solvent gave a residue, which was chromatographed on a column of silica gel eluting with ethyl acetate/hexane (1:1) to give 6.3 g (64%) of the title compound as clear colorless oil.

Workup

  1. customThe reaction mixture was quenched with saturated aqueous sodium bicarbonate (150 mL)
  2. extractionextracted with CH2Cl2 (30 mL×2)
  3. dry with materialthe combined organic layer was dried over sodium sulfate
  4. filtrationfiltered
  5. customRemoval of the solvent
  6. customgave a residue, which
  7. customwas chromatographed on a column of silica gel eluting with ethyl acetate/hexane (1:1)

Sources & evidence

ORD record
ord-e3129407928e426e84ac3271b4a361e4
Source dataset
uspto-grants-2009_09
Patent number
US07589109B2

Reaction notes

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