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

HRID 1712365Notes

Reaction equation

HRID 1712365 reaction equation
C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].Cl[CH:29]([O:42][CH:43]1[CH:48]([C:49]2[CH:54]=[CH:53][C:52]([O:55][CH2:56][CH2:57][CH2:58][O:59][CH2:60][C:61]3[CH:66]=[CH:65][CH:64]=[CH:63][C:62]=3[O:67][CH3:68])=[CH:51][CH:50]=2)[CH2:47][CH2:46][N:45]([C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[CH2:44]1)[C:30]1[CH:35]=[CH:34][CH:33]=[C:32]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[CH:31]=1.[NH:76]1[CH2:81][CH2:80][O:79][CH2:78][CH2:77]1>C1(C)C=CC=CC=1>[CH3:68][O:67][C:62]1[CH:63]=[CH:64][CH:65]=[CH:66][C:61]=1[CH2:60][O:59][CH2:58][CH2:57][CH2:56][O:55][C:52]1[CH:53]=[CH:54][C:49]([CH:48]2[CH2:47][CH2:46][N:45]([C:69]([O:71][C:72]([CH3:75])([CH3:74])[CH3:73])=[O:70])[CH2:44][CH:43]2[O:42][CH2:29][C:30]2[CH:35]=[CH:34][C:33]([N:76]3[CH2:81][CH2:80][O:79][CH2:78][CH2:77]3)=[C:32]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[CH:31]=2)=[CH:50][CH:51]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxideHCID 68499192Tert-butyl 3-[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-[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-5a4f038b69cb4364af55f1166a26a8d8
Source dataset
uspto-grants-2010_09
Patent number
US07790715B2

Reaction notes

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