Water → Benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-pyrrolidin-1-ylphenyl)piperidine-1-carboxylate

HRID 1176584Notes

Reaction equation

HRID 1176584 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:11]2[CH:12]=[C:13]([CH2:16][O:17][CH:18]3[CH:23]([C:24]4[CH:29]=[CH:28][C:27](OS(C(F)(F)F)(=O)=O)=[CH:26][CH:25]=4)[CH2:22][CH2:21][N:20]([C:38]([O:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[O:39])[CH2:19]3)[CH:14]=[CH:15][C:10]=2[O:9][CH2:8][CH2:7]1.[NH:48]1[CH2:52][CH2:51][CH2:50][CH2:49]1.C(=O)([O-])[O-].[Cs+].[Cs+].O>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:11]2[CH:12]=[C:13]([CH2:16][O:17][CH:18]3[CH:23]([C:24]4[CH:25]=[CH:26][C:27]([N:48]5[CH2:52][CH2:51][CH2:50][CH2:49]5)=[CH:28][CH:29]=4)[CH2:22][CH2:21][N:20]([C:38]([O:40][CH2:41][C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)=[O:39])[CH2:19]3)[CH:14]=[CH:15][C:10]=2[O:9][CH2:8][CH2:7]1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 31268PyrrolidineHCID 86610023benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-trifluoromethanesulphonyloxyphenyl)piperidin-1-carboxylate

Product 1

HCID 68503530Benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-pyrrolidin-1-ylphenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

The mixture of 0.300 g of benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-trifluoromethanesulphonyloxyphenyl)piperidine-1-carboxylate, 0.043 ml of pyrrolidine, 0.041 g of (i)-2,2′-bis(diphenylphosphine)-1,1′-binaphthyl, 0.194 g of caesium carbonate and 0.0099 g of palladium(II) acetate in 3.0 ml of dioxane is stirred under argon at 100° C. over 20 hours. The reaction mixture is cooled, admixed with water (20 ml) and extracted with tert-butyl methyl ether (2×20 ml). The organic phases are washed successively with water (20 ml) and brine (20 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a slightly yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.40 (2:1 EtOAc-heptane); Rt=4.68.

Workup

  1. temperatureThe reaction mixture is cooled
  2. extractionextracted with tert-butyl methyl ether (2×20 ml)
  3. washThe organic phases are washed successively with water (20 ml) and brine (20 ml)
  4. dry with materialdried over sodium sulphate
  5. filtrationfiltered
  6. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-807ed43ba0474e279260b1ef606d6c7c
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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