Hydrochloric Acid → HCID 69107963, compound

HRID 657657Notes

Reaction equation

HRID 657657 reaction equation
[Cl:1][CH2:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][N+:15]([O-:18])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].C(O)(=O)C(C1C=CC=CC=1)O.[CH3:36][C@H:37]1[CH2:42][CH2:41][CH2:40][NH:39][CH2:38]1.Cl>CN(C)C=O.C(O)C.C(N(CC)CC)C>[ClH:1].[CH3:36][C@H:37]1[CH2:42][CH2:41][CH2:40][N:39]([CH2:2][CH2:3][CH2:4][O:5][C:6]2[CH:11]=[CH:10][C:9]([C:12]3[CH:17]=[CH:16][N+:15]([O-:18])=[CH:14][CH:13]=3)=[CH:8][CH:7]=2)[CH2:38]1

Participants

8

Reactant 4

HCID 313Hydrochloric Acid2×HCID 11430Potassium CarbonateHCID 13929038HCID 13929038, compound2×HCID 23150273HCID 23150273, compound

Product 1

HCID 69107963HCID 69107963, compoundYield 23.6%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a solution of 4-[4-(3-chloropropoxy)phenyl]pyridine 1-oxide (231 mg) and triethylamine (366 μL) in N,N-dimethylformamide (5 mL) are added potassium carbonate (363 mg) and (3S)-3-methylpiperidine mandelate (264 mg). The mixture is stirred at a temperature close to 60° C. for four hours. An additional amount of (3S)-3-methylpiperidine mandelate (100 mg) is added and heating is continued overnight. The suspension is filtered and the precipitate washed with ethyl acetate. The combined organic phases are concentrated under reduced pressure. The residue is purified twice by column chromatography over silica gel using a gradient dichloromethane/methanol/triethylamine from 100/0/0 to 95/5/0.1. Fractions containing the expected product are pooled and concentrated under reduced pressure to give 90 mg of the crude base which is converted to the hydrochloride with an ethereal solution of hydrogen chloride in ethanol to give 75 mg of (3S)-4-{4-[3-(3-methylpiperidin-1-yl)propoxy]phenyl}pyridine 1-oxide, hydrochloride melting at 74° C.

Workup

  1. customclose to 60° C. for four hours
  2. temperatureheating
  3. filtrationThe suspension is filtered
  4. washthe precipitate washed with ethyl acetate
  5. concentrationThe combined organic phases are concentrated under reduced pressure
  6. customThe residue is purified twice by column chromatography over silica gel using a gradient dichloromethane/methanol/triethylamine from 100/0/0 to 95/5/0.1
  7. additionFractions containing the expected product
  8. concentrationconcentrated under reduced pressure
  9. customto give 90 mg of the crude base which

Sources & evidence

ORD record
ord-2b9bce58c73449bb8f5c62a9f2b51f14
Source dataset
uspto-grants-2011_12
Patent number
US08076329B2

Reaction notes

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