alpha-Chloro-m-nitrotoluene → 1-Methyl-4-[(3-nitrophenyl)methoxy]piperidine

HRID 639415Notes

Reaction equation

HRID 639415 reaction equation
[OH:1][CH:2]1[CH2:7][CH2:6][N:5]([CH3:8])[CH2:4][CH2:3]1.[OH-].[Na+].[N+:11]([C:14]1[CH:15]=[C:16]([CH:19]=[CH:20][CH:21]=1)[CH2:17]Cl)([O-:13])=[O:12]>ClCCl.O.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[CH3:8][N:5]1[CH2:6][CH2:7][CH:2]([O:1][CH2:17][C:16]2[CH:19]=[CH:20][CH:21]=[C:14]([N+:11]([O-:13])=[O:12])[CH:15]=2)[CH2:3][CH2:4]1

Participants

7

Reactant 3

HCID 12078alpha-Chloro-m-nitrotolueneHCID 14798Sodium HydroxideHCID 660484-Piperidinol, 1-methyl-

Product 1

HCID 685663511-Methyl-4-[(3-nitrophenyl)methoxy]piperidine

Reagents, catalysts & solvents 3

HCID 66133Benzyl triethylammonium chlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

4-Hydroxy-1-methylpiperidine (11.5 g, 0.1 mol) is dissolved in 250 mL dichloromethane. A solution of 100 g NaOH in 100 mL of water is added followed by 17.2 g (0.1 mol) 3-nitro-benzylchloride and a catalytic amount of benzyl-triethylammonium chloride. The mixture is stirred very efficiently during 2 h at rt and then poured into 300 mL of ice-cold water. The organic layer is separated and the organic phase extracted once more with dichloromethane. The organic phase is extracted with 1N HCl (2×200 mL) and the aqueous extracts adjusted to pH 9-10 by the addition of solid sodium carbonate. The basic solution is extracted with ethyl acetate (2×200 mL) and the organic phase washed with brine, dried over potassium carbonate and evaporated. 1-Methyl-4-(3-nitro-benzyloxy)-piperidine is obtained as brown viscous oil. HPLC: 1.35 (System XS); [M+H]+ 251.0.

Workup

  1. customThe organic layer is separated
  2. extractionthe organic phase extracted once more with dichloromethane
  3. extractionThe organic phase is extracted with 1N HCl (2×200 mL)
  4. additionthe aqueous extracts adjusted to pH 9-10 by the addition of solid sodium carbonate
  5. extractionThe basic solution is extracted with ethyl acetate (2×200 mL)
  6. washthe organic phase washed with brine
  7. dry with materialdried over potassium carbonate
  8. customevaporated

Sources & evidence

ORD record
ord-4960d95561bc4536a8f87c9442ef1912
Source dataset
uspto-grants-2010_04
Patent number
US07691855B2

Reaction notes

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