Diisopropylethylamine → Benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-[4-(4-methylcarbamoylbut-1-ynyl)phenyl]piperidine-1-carboxylate

HRID 1176659Notes

Reaction equation

HRID 1176659 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.[CH3:48][NH:49][C:50]([CH2:52][CH2:53][CH2:54][C:55]#C)=[O:51].C(N(CC)C(C)C)(C)C.C(=O)([O-])O.[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CN(C)C=O>[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]([C:55]#[C:54][CH2:53][CH2:52][C:50](=[O:51])[NH:49][CH3:48])=[CH:28][CH:29]=4)[CH2:22][CH2:21][N:20]([C:38]([O:40][CH2:41][C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)=[O:39])[CH2:19]3)[CH:14]=[CH:15][C:10]=2[O:9][CH2:8][CH2:7]1

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 14342989N-methylpent-4-ynecarboxamideHCID 86610023benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-(4-trifluoromethanesulphonyloxyphenyl)piperidin-1-carboxylate

Product 1

HCID 68498993Benzyl 3-[4-(3-methoxypropyl)-3,4-dihydro-2H-benzo[1,4]oxazin-6-ylmethoxy]-4-[4-(4-methylcarbamoylbut-1-ynyl)phenyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

The mixture of 0.124 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), 0.0305 g of N-methylpent-4-ynecarboxamide, 0.0797 g of N,N-diisopropylethylamine, 0.0136 g of bis(triphenylphosphine)palladium(II) chloride, 0.0038 g of copper(I) iodide and 1.0 ml of N,N-dimethylformamide is stirred under argon at 45° C. over 36 hours. The reaction mixture is cooled, poured onto saturated aqueous sodium hydrogencarbonate solution (20 ml) and extracted with ethyl acetate (2×50 ml). The combined organic phases are washed with brine (30 ml), dried over sodium sulphate and concentrated by evaporation. The title compound is obtained as a yellowish oil from the residue by means of flash chromatography (SiO2 60F). Rf=0.23 (EtOAc); Rt=4.86.

Workup

  1. temperatureThe reaction mixture is cooled
  2. extractionextracted with ethyl acetate (2×50 ml)
  3. washThe combined organic phases are washed with brine (30 ml)
  4. dry with materialdried over sodium sulphate
  5. concentrationconcentrated by evaporation

Sources & evidence

ORD record
ord-98350aea068a48e4ba8a445a3a773dc1
Source dataset
uspto-grants-2010_11
Patent number
US07842688B2

Reaction notes

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