Cesium carbonate → HCID 68325410, compound

HRID 2403275Notes

Reaction equation

HRID 2403275 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:19]=[CH:18][C:17]([NH2:20])=[CH:16][CH:15]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].Cl[C:22]1[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]2[CH:15]=[CH:16][C:17]([NH:20][C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][N:23]=3)=[CH:18][CH:19]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 276852,5-DichloropyridineHCID 58315596tert-Butyl 2-(4-aminophenyl)morpholine-4-carboxylate

Product 1

HCID 68325410HCID 68325410, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

(RS)-2-(4-Amino-phenyl)-morpholine-4-carboxylic acid tert-butyl ester (60 mg, CAS 1002726-96-6), 2,5-dichloropyridine (31.9 mg, CAS 16110-09-1) and cesium carbonate (105 mg) were combined with dioxane (2 ml) to give a yellow suspension. The mixture was degassed by bubbling argon into the mixture for several minutes. Xantphos (7.48 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (6.69 mg) were then added. The reaction mixture was then capped and stirred at 100° C. overnight. The crude reaction mixture was cooled to room temperature and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography (silica gel; gradient: 0% to 70% EtOAc in hexanes) to afford (RS)-2-[4-(5-chloro-pyridin-2-ylamino)-phenyl]-morpholine-4-carboxylic acid tert-butyl ester (52 mg, 62%) as a yellow amorphous solid. MS (ISP): 392.0 ([{37Cl}M+H]+), 390.1 ([{35Cl}M+H]+), 336.4 ([{37Cl}M+H—C4H8]+), 334.3 ([{35Cl}M+H—C4H8]+).

Workup

  1. customto give a yellow suspension
  2. customThe mixture was degassed
  3. customby bubbling argon into the mixture for several minutes
  4. additionXantphos (7.48 mg) and tris(dibenzylideneacetone)dipalladium chloroform complex (6.69 mg) were then added
  5. customThe reaction mixture was then capped
  6. customThe crude reaction mixture
  7. temperaturewas cooled to room temperature
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by flash column chromatography (silica gel; gradient: 0% to 70% EtOAc in hexanes)

Sources & evidence

ORD record
ord-326e97f3eaec461b84bb197b6911ec61
Source dataset
uspto-grants-2014_08
Patent number
US08802673B2

Reaction notes

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