Biphenyl → Benzyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-[3-(3-methoxypropoxy)-4-pyrrolidin-1-ylbenzyloxy]piperidine-1-carboxylate

HRID 1712362Notes

Reaction equation

HRID 1712362 reaction equation
C1(C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+].Br[C:20]1[CH:63]=[CH:62][C:23]([CH2:24][O:25][CH:26]2[CH:31]([C:32]3[CH:37]=[CH:36][C:35]([O:38][CH2:39][CH2:40][CH2:41][O:42][CH2:43][C:44]4[CH:49]=[CH:48][CH:47]=[CH:46][C:45]=4[O:50][CH3:51])=[CH:34][CH:33]=3)[CH2:30][CH2:29][N:28]([C:52]([O:54][CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)=[O:53])[CH2:27]2)=[CH:22][C:21]=1[O:64][CH2:65][CH2:66][CH2:67][O:68][CH3:69].[NH:70]1[CH2:74][CH2:73][CH2:72][CH2:71]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:51][O:50][C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][C:44]=1[CH2:43][O:42][CH2:41][CH2:40][CH2:39][O:38][C:35]1[CH:36]=[CH:37][C:32]([CH:31]2[CH2:30][CH2:29][N:28]([C:52]([O:54][CH2:55][C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][CH:57]=3)=[O:53])[CH2:27][CH:26]2[O:25][CH2:24][C:23]2[CH:62]=[CH:63][C:20]([N:70]3[CH2:74][CH2:73][CH2:72][CH2:71]3)=[C:21]([O:64][CH2:65][CH2:66][CH2:67][O:68][CH3:69])[CH:22]=2)=[CH:33][CH:34]=1

Participants

7

Reactant 4

HCID 7095BiphenylHCID 31268PyrrolidineHCID 23676156Sodium t-butoxideHCID 68501756Benzyl 3-[4-bromo-3-(3-methoxypropoxy)benzyloxy]-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 68505857Benzyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-[3-(3-methoxypropoxy)-4-pyrrolidin-1-ylbenzyloxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

The mixture of 0.019 g of 2-di-t-butylphosphino)biphenyl, 0.005 g of palladium(II) acetate and 0.134 g of sodium tert-butoxide is admixed under argon with the solution of 0.831 g of benzyl 3-[4-bromo-3-(3-methoxypropoxy)benzyloxy]-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate and 0.100 ml of pyrrolidine in 7.0 ml of toluene. The reaction mixture is stirred at 90° C. over 16 hours, subsequently cooled, poured onto water (40 ml) and extracted with tert-butyl methyl ether (2×40 ml). The organic phases are washed with brine (40 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a white foam from the residue by means of flash chromatography (SiO2 60F). Rf=0.22 (1:1 EtOAc-heptane); Rt=5.40.

Workup

  1. temperaturesubsequently cooled
  2. additionpoured onto water (40 ml)
  3. extractionextracted with tert-butyl methyl ether (2×40 ml)
  4. washThe organic phases are washed with brine (40 ml)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-a278ab4c3d0c4689a3cbf72f3a6d77cb
Source dataset
uspto-grants-2010_09
Patent number
US07790715B2

Reaction notes

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