Methyl iodide → Tert-butyl 4-(3-methoxy-4-(methoxycarbonyl)phenoxy)piperidine-1-carboxylate

HRID 128581Notes

Reaction equation

HRID 128581 reaction equation
[OH:1][C:2]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[H-].[Na+].I[CH3:29]>C1COCC1.C(OCC)(=O)C>[CH3:29][O:1][C:2]1[CH:11]=[C:10]([O:12][CH:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:15][CH2:14]2)[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5]

Participants

6

Reactant 3

HCID 6328Methyl iodide4×HCID 24758Sodium hydride3×HCID 105940774-(N-t-Butoxycarbonyl-4-piperidinyloxy)-2-hydroxybenzoic acid methyl ester

Product 1

HCID 10570851Tert-butyl 4-(3-methoxy-4-(methoxycarbonyl)phenoxy)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Methyl 2-hydroxy-4-(1-Boc-4-piperidyloxy)benzoate (6.7 g, 19.1 mmol) was dissolved in THF (20 ml) and stirred in an ice bath under nitrogen. Sodium hydride (1.17g of a 60% suspension in mineral oil, 29.5 mmol) was added and the mixture was stirred for 15 min in the cold, then for 15 min at ambient temperature. Iodomethane (2.4 ml, 5.47 g, 38.1 mmol) was added and the mixture was allowed to stir at ambient temperature under nitrogen for 72 hours. An additional 0.51 g of 60% sodium hydride suspension was added and the mixture stirred an additional 7 hours, then an additional 1.2 ml of iodomethane was added and the mixture stirred another 18 hours. An additional 0.53 g of sodium hydride suspension was added, the mixture was stirred 1.5 hours, then an additional 1 ml of iodomethane was added and the mixture stirred 6 hours. An additional 1 ml of iodomethane was added and the mixture stirred 18 hours at ambient temperature. The mixture was diluted with ethyl acetate and washed with saturated aqueous sodium bicarbonate and with brine. The organic layer was dried over sodium sulfate, filtered, and evaporated to dryness in vacuo to give methyl 2-methoxy-4-(1-Boc-4-piperidyloxy)-benzoate.

Workup

  1. stirringthe mixture was stirred for 15 min in the cold, then for 15 min at ambient temperature
  2. stirringto stir at ambient temperature under nitrogen for 72 hours
  3. stirringthe mixture stirred an additional 7 hours
  4. stirringthe mixture stirred another 18 hours
  5. stirringthe mixture was stirred 1.5 hours
  6. stirringthe mixture stirred 6 hours
  7. stirringthe mixture stirred 18 hours at ambient temperature
  8. washwashed with saturated aqueous sodium bicarbonate and with brine
  9. dry with materialThe organic layer was dried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-86dd1c314f524ba28dafcbba610d56fa
Source dataset
uspto-grants-1995_11
Patent number
US05464788

Reaction notes

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