Potassium Carbonate → Tert-butyl 3-hydroxy-4-{4-[3-(2-methoxybenzyloxy) propoxy]phenyl}piperidine-1-carboxylate

HRID 1858772Notes

Reaction equation

HRID 1858772 reaction equation
[OH:1][CH:2]1[CH:7]([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1.Cl[CH2:23][CH2:24][CH2:25][O:26][CH2:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1[O:34][CH3:35].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[OH:1][CH:2]1[CH:7]([C:8]2[CH:9]=[CH:10][C:11]([O:14][CH2:23][CH2:24][CH2:25][O:26][CH2:27][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=3[O:34][CH3:35])=[CH:12][CH:13]=2)[CH2:6][CH2:5][N:4]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:3]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 113449261-(3-Chloro-propoxymethyl)-2-methoxy-benzeneHCID 21713087(3S,4S)-tert-Butyl 3-hydroxy-4-(4-hydroxyphenyl)piperidine-1-carboxylate

Product 1

HCID 15546933Tert-butyl 3-hydroxy-4-{4-[3-(2-methoxybenzyloxy) propoxy]phenyl}piperidine-1-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

(α) A solution of 5.2 g (17.7 mmol) of tert-butyl (3RS,4RS)-3-hydroxy-4-(4-hydroxy-phenyl)-piperidine-1-carboxylate [Example 46(b)] and 3.37 ml (3.8 g,17.7 mmol) of 2-methoxybenzyl 3-chloropropyl ether in 18 ml of absolute DMF was treated with 3.7 g (26.9 mmol) of anhydrous potassium carbonate and stirred at 120° C. for 60 h. For the working-up, the reaction mixture was partitioned between 250 ml of water and 250 ml of ethyl acetate. The organic phase was separated and the aqueous phase was extracted three times with 100 ml of ethyl acetate each time. The combined organic phases were washed twice with 100 ml of water each time and finally the solvent was distilled off under reduced pressure. The crude product was crystallized by treatment with ether. There were obtained 7.3 g (88% of theory) of tert-butyl (3RS,4RS)-3-hydroxy-4-[4-[3-(2-methoxy-benzyloxy)-propoxy]-phenyl]-piperidine-1-carboxylate as a colourless solid; MS: 472 (M+H)+.

Workup

  1. customthe reaction mixture was partitioned between 250 ml of water and 250 ml of ethyl acetate
  2. customThe organic phase was separated
  3. extractionthe aqueous phase was extracted three times with 100 ml of ethyl acetate each time
  4. washThe combined organic phases were washed twice with 100 ml of water each time
  5. distillationfinally the solvent was distilled off under reduced pressure
  6. customThe crude product was crystallized by treatment with ether

Sources & evidence

ORD record
ord-1687284a14474edbbf35cef0e9286356
Source dataset
uspto-grants-2000_11
Patent number
US06150526

Reaction notes

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