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

HRID 1176337Notes

Reaction equation

HRID 1176337 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].Br[C:29]1[CH:72]=[CH:71][C:32]([CH2:33][O:34][CH:35]2[CH:40]([C:41]3[CH:46]=[CH:45][C:44]([O:47][CH2:48][CH2:49][CH2:50][O:51][CH2:52][C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][C:54]=4[O:59][CH3:60])=[CH:43][CH:42]=3)[CH2:39][CH2:38][N:37]([C:61]([O:63][CH2:64][C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[O:62])[CH2:36]2)=[CH:31][C:30]=1[O:73][CH2:74][CH2:75][CH2:76][O:77][CH3:78].[NH:79]1[CH2:83][CH2:82][CH2:81][CH2:80]1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:60][O:59][C:54]1[CH:55]=[CH:56][CH:57]=[CH:58][C:53]=1[CH2:52][O:51][CH2:50][CH2:49][CH2:48][O:47][C:44]1[CH:45]=[CH:46][C:41]([CH:40]2[CH2:39][CH2:38][N:37]([C:61]([O:63][CH2:64][C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[O:62])[CH2:36][CH:35]2[O:34][CH2:33][C:32]2[CH:71]=[CH:72][C:29]([N:79]3[CH2:83][CH2:82][CH2:81][CH2:80]3)=[C:30]([O:73][CH2:74][CH2:75][CH2:76][O:77][CH3:78])[CH:31]=2)=[CH:42][CH:43]=1

Participants

7

Reactant 4

HCID 31268PyrrolidineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 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-ad903a9c0e144f57a0bb4d4700808659
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

Loading…