Sodium Bicarbonate → Benzyl 4-{4-[3-(2,5-difluorophenoxy)propylamino]phenyl}-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

HRID 1712594Notes

Reaction equation

HRID 1712594 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.[F:48][C:49]1[CH:59]=[CH:58][C:57]([F:60])=[CH:56][C:50]=1[O:51][CH2:52][CH2:53][CH2:54][NH2:55].C(=O)([O-])O.[Na+]>O1CCOCC1.Cl[Pd-](P(C1CC2CC1CC2)C1CC2CC1CC2)[C-]1C=CC=C1CN(C)C.[CH-]1C=CC=C1.[Fe+2]>[F:48][C:49]1[CH:59]=[CH:58][C:57]([F:60])=[CH:56][C:50]=1[O:51][CH2:52][CH2:53][CH2:54][NH:55][C:27]1[CH:28]=[CH:29][C:24]([CH:23]2[CH2:22][CH2:21][N:20]([C:38]([O:40][CH2:41][C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)=[O:39])[CH2:19][CH:18]2[O:17][CH2:16][C:13]2[CH:14]=[CH:15][C:10]3[O:9][CH2:8][CH2:7][N:6]([CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:11]=3[CH:12]=2)=[CH:25][CH:26]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 632690273-(2,5-Difluorophenoxy)propan-1-amineHCID 86610023benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-trifluoromethanesulphonyloxyphenyl)piperidin-1-carboxylate

Product 1

HCID 68503180Benzyl 4-{4-[3-(2,5-difluorophenoxy)propylamino]phenyl}-3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 178483166HCID 178483166, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A baked-out Schlenk flask is initially charged with 0.350 g of chloro(di-2-norbomylphosphino)(2-dimethylaminomethylferrocen-1-yl)palladium(II). Under argon, a solution of 0.520 g of benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-trifluoromethanesulphonyloxyphenyl)piperidine-1-carboxylate (Example 265b) and 0.172 g of 3-(2,5-difluorophenoxy)propylamine in 5.3 ml of dried dioxane is added. The reaction mixture is stirred at room temperature over 30 minutes and subsequently at 100° C. over 18 hours. The reaction mixture is cooled, poured onto aqueous 1M sodium hydrogencarbonate solution (20 ml) and extracted with tert-butyl methyl ether (2×20 ml). The organic phases are washed with brine (1×20 ml), dried over sodium sulphate, filtered and concentrated by evaporation. The title compound is obtained as a colourless oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.29 (2:1 EtOAc-heptane); Rt=4.91.

Workup

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

Sources & evidence

ORD record
ord-94c3ea3b1aa4478a8675faded2c47852
Source dataset
uspto-grants-2010_09
Patent number
US07790715B2

Reaction notes

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