Cesium carbonate → (R)-3-(4-bromo-2,6-dimethylphenoxymethyl)-1-methylpiperidine

HRID 1872671Notes

Reaction equation

HRID 1872671 reaction equation
S([O:11][CH2:12][C@@H:13]1[CH2:18][CH2:17][CH2:16][N:15]([CH3:19])[CH2:14]1)(C1C=CC(C)=CC=1)(=O)=O.[Br:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24](O)=[C:23]([CH3:29])[CH:22]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[Br:20][C:21]1[CH:26]=[C:25]([CH3:27])[C:24]([O:11][CH2:12][C@@H:13]2[CH2:18][CH2:17][CH2:16][N:15]([CH3:19])[CH2:14]2)=[C:23]([CH3:29])[CH:22]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 169194-Bromo-2,6-dimethylphenolHCID 15895222(R)-3-tosyloxymethyl-1-methylpiperidine

Product 1

HCID 15895221(R)-3-(4-bromo-2,6-dimethylphenoxymethyl)-1-methylpiperidine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Alternatively, a solution of (R)-3-tosyloxymethyl-1 -methylpiperidine (100 mg, 0.35 mmol), 4-bromo-2,6-dimethylphenol (75 mg, 0.37 mmol), and cesium carbonate (240 mg, 0.74 mmol) in dimethylformamide (4 mL) was heated to 65° C. under a nitrogen atmosphere for 1.5 hours. The solution was cooled to room temperature and partitioned between ethyl acetate (50 mL) and water (30 mL). The organic layer was removed and the aqueous phase extracted once more with ethyl acetate (30 mL). The combined acetate layers were dried over magnesium sulfate and concentrated to afford the (R)-3-(4-bromo-2,6-dimethylphenoxymethyl)-1-methylpiperidine as a clear oil. This material was identical to that prepared in Example 2E when analyzed by chiral HPLC (Chiralpak AD, 97:3:0.1 hexane/2-propanol/diethylamine).

Workup

  1. custompartitioned between ethyl acetate (50 mL) and water (30 mL)
  2. customThe organic layer was removed
  3. extractionthe aqueous phase extracted once more with ethyl acetate (30 mL)
  4. dry with materialThe combined acetate layers were dried over magnesium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-1071dc23cefa46b38f5956e4c97cda02
Source dataset
uspto-grants-2000_08
Patent number
US06110937

Reaction notes

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