Ammonium Chloride → Tert-butyl 4-acetyl-4-methoxypiperidine-1-carboxylate

HRID 8755Notes

Reaction equation

HRID 8755 reaction equation
CO[C:3]([C:5]1([O:18][CH3:19])[CH2:10][CH2:9][N:8]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:7][CH2:6]1)=[O:4].[CH3:20][Si](C[Li])(C)C.[Cl-].[NH4+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)C.C(OCC)(=O)C.O>[C:3]([C:5]1([O:18][CH3:19])[CH2:6][CH2:7][N:8]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:9][CH2:10]1)(=[O:4])[CH3:20]

Participants

9

Reactant 4

HCID 25517Ammonium ChlorideHCID 2724141Tetrabutylammonium FluorideHCID 219840121-tert-Butyl 4-methyl 4-methoxypiperidine-1,4-dicarboxylateHCID 178418939HCID 178418939, compound2×

Product 1

HCID 21983927Tert-butyl 4-acetyl-4-methoxypiperidine-1-carboxylateYield 37.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-tert-butyl 4-methoxycarbonyl-4-methoxypiperidine-1-carboxylate (2.5 g, 9.05 mmol) dissolved in 100 mL of tetrahydrofuran at −78° C. was added trimethylsilylmethyl lithium (23 mL, 23 mmol). After 30 min additional trimethylsilylmethyl lithium (2.7 mL, 2.7 mmol) was added. The reaction mixture was then diluted with diethyl ether, poured into saturated ammonium chloride, and extracted three times with diethyl ether. The organic layers were combined, washed with saturated sodium chloride, dried over sodium sulfate, filtered and concentrated. The residue was purified by flash chromatography eluting with 10% ethyl acetate/hexanes to afford 1.7 g of silyl product which was taken up in tetrahydrofuran (50 mL) and tetrabutylammonium fluoride (6.1 mL, 6.1 mmol) was added. After 30 min at room temperature, the reaction mixture was diluted with ethyl acetate, poured into water, and extracted three times with ethyl acetate. The organic layers were combined, washed with sodium chloride solution, dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography to afford the title compound (0.863 g).

Workup

  1. extractionextracted three times with diethyl ether
  2. washwashed with saturated sodium chloride
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography
  7. washeluting with 10% ethyl acetate/hexanes
  8. customto afford 1.7 g of silyl product which
  9. extractionextracted three times with ethyl acetate
  10. washwashed with sodium chloride solution
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-51623ca6fed2402986932fa772644519
Source dataset
uspto-grants-2006_08
Patent number
US07091211B2

Reaction notes

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