Cesium carbonate → HCID 89602751, compound

HRID 2174586Notes

Reaction equation

HRID 2174586 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][N:3]=1.[NH:9]1[CH2:12][CH2:11][C:10]1=[O:13].C([O-])([O-])=O.[Cs+].[Cs+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([N:9]2[CH2:12][CH2:11][C:10]2=[O:13])=[N:3][CH:4]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 693532,5-DibromopyridineHCID 1367212-Azetidinone

Product 1

HCID 89602751HCID 89602751, compoundYield 62.6%

Reagents, catalysts & solvents 3

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

A solution of 2,5-dibromopyridine (500 mg, 2.10 mmol), 2-azetidinone (140 mg, 1.97 mmol) and Cs2CO3 (1.27 g, 3.89 mmol) in toluene (15 ml) was added Pd2(dba)3 (36 mg, 0.039 mmol), Xantphos (45 mg, 0.078 mmol) and the reaction mixture was purged with nitrogen for 10 minutes, then was heated at 90° C. for 18 h in seal tube. The progress of the reaction was monitored by TLC. After 18 h of stirring, the mixture was cooled to 20-35° C., filtered on celite and concentrated. The resultant residue was diluted with water (50 ml) and extracted with ethyl acetate (2×50 ml). The combined organic layers were washed with brine (50 ml), followed by drying over anhydrous Na2SO4 and filtering. The filtrate was rotary evaporated to get residue which was purified by column chromatography using a mixture of 50% ethyl acetate/pet ether as an eluent to get the desired compound as a creamy white solid (280 mg, 59%). 1H NMR (400 MHz, DMSO-d6) δ 8.33 (d, J=1.9 Hz, 1H), 7.76 (dd, J=8.8, 2.5 Hz, 1H), 7.67 (d, J=8.8 Hz, 1H), 3.78 (t, J=4.9 Hz, 2H), 3.13 (t, J=4.9 Hz, 2H); MS (ES) m/e 229.0 (M+2H)+.

Workup

  1. customthe reaction mixture was purged with nitrogen for 10 minutes
  2. temperaturethe mixture was cooled to 20-35° C.
  3. filtrationfiltered on celite
  4. concentrationconcentrated
  5. additionThe resultant residue was diluted with water (50 ml)
  6. extractionextracted with ethyl acetate (2×50 ml)
  7. washThe combined organic layers were washed with brine (50 ml)
  8. dry with materialby drying over anhydrous Na2SO4
  9. filtrationfiltering
  10. customThe filtrate was rotary evaporated
  11. customto get residue which
  12. customwas purified by column chromatography
  13. additiona mixture of 50% ethyl acetate/pet ether as an eluent

Sources & evidence

ORD record
ord-7debe14683ca4bdbb8272feb7fdf3447
Source dataset
uspto-grants-2015_06
Patent number
US09062002B2

Reaction notes

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