Morpholine → tert-Butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-[3-(3-methoxypropoxy)-4-morpholin-4-ylbenzyloxy]piperidine-1-carboxylate

HRID 1176340Notes

Reaction equation

HRID 1176340 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].Cl[C:29]1[CH:69]=[CH:68][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][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:36]2)=[CH:31][C:30]=1[O:70][CH2:71][CH2:72][CH2:73][O:74][CH3:75].[NH:76]1[CH2:81][CH2:80][O:79][CH2:78][CH2:77]1>C1(C)C=CC=CC=1>[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][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:36][CH:35]2[O:34][CH2:33][C:32]2[CH:68]=[CH:69][C:29]([N:76]3[CH2:81][CH2:80][O:79][CH2:78][CH2:77]3)=[C:30]([O:70][CH2:71][CH2:72][CH2:73][O:74][CH3:75])[CH:31]=2)=[CH:42][CH:43]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 68504735Tert-butyl 3-[4-chloro-3-(3-methoxypropoxy)benzyloxy]-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate

Product 1

HCID 68499477tert-Butyl 4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}-3-[3-(3-methoxypropoxy)-4-morpholin-4-ylbenzyloxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
110 °C

Procedure

The mixture of 0.0074 g of 2-(di-t-butylphosphino)biphenyl, 0.017 g of dipalladiumtris (dibenzylidenacetone)-chloroform complex and 0.055 g of sodium tert-butoxide is admixed under argon with the solution of 0.280 g of tert-butyl 3-[4-chloro-3-(3-methoxypropoxy)benzyloxy]-4-{4-[3-(2-methoxybenzyloxy)propoxy]phenyl}piperidine-1-carboxylate (Example 31a) and 0.043 ml of morpholine in 2.0 ml of toluene. The reaction mixture is stirred at 110° C. over 16 hours, subsequently cooled, poured onto water (20 ml) and extracted with ethyl acetate (2×20 ml). The organic phases are washed with brine (20 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=0.23 (2:1 EtOAc-heptane); Rt=5.46.

Workup

  1. temperaturesubsequently cooled
  2. additionpoured onto water (20 ml)
  3. extractionextracted with ethyl acetate (2×20 ml)
  4. washThe organic phases are washed with brine (20 ml)
  5. dry with materialdried over sodium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-069e2e28574e4e2697c41cbf9bbf0f62
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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