Sodium Carbonate → HCID 51029555, compound

HRID 1516380Notes

Reaction equation

HRID 1516380 reaction equation
Br[C:2]1[C:3]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[N:4][CH:5]=[C:6]([CH:17]=1)[C:7]([NH:9][C@@H:10]1[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]1[OH:16])=[O:8].[Cl:24][C:25]1[CH:26]=[C:27](B(O)O)[CH:28]=[CH:29][C:30]=1[Cl:31].C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CN(C=O)C.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(Cl)Cl>[Cl:24][C:25]1[CH:26]=[C:27]([C:2]2[C:3]([O:18][CH2:19][C:20]([F:23])([F:22])[F:21])=[N:4][CH:5]=[C:6]([CH:17]=2)[C:7]([NH:9][C@@H:10]2[CH2:15][CH2:14][CH2:13][CH2:12][C@H:11]2[OH:16])=[O:8])[CH:28]=[CH:29][C:30]=1[Cl:31]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27343303,4-Dichlorobenzeneboronic acidHCID 69812169HCID 69812169, compound

Product 1

HCID 51029555HCID 51029555, compound

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

5-Bromo-N-((1R,2R)-2-hydroxy-cyclohexyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide (59.8 g, 151 mmol) was dissolved in toluene (2500 mL) and DMF (200 mL). To this solution was added with stirring [1,1′-bis(diphenylphosphino)ferrocene]-dichloropalladium(II) CH2Cl2 (6.15 g, 7.5 mmol), 3,4-dichlorophenylboronic acid (30.2 g, 158 mmol) and sodium carbonate solution (2M, 150 mL). This mixture was heated to 90° C. for 2 h, cooled to room temperature and filtered through diatomaceous earth. The filter cake was thoroughly washed with ethyl acetate (3000 mL). The filtrates were combined, washed twice with water (2×2000 mL), and the water phases were extracted with ethyl acetate (2×1500 mL). Organic phases were pooled, dried with MgSO4 and the volatiles removed in vacuo. The residue was purified by filtration through silica (500 g) with ethyl acetate. The solvent was removed and the residue was triturated with diethyl ether to give after drying in vacuo the title compound (45.6 g) as a grayish solid; MS 463.079, 465.077 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through diatomaceous earth
  3. washThe filter cake was thoroughly washed with ethyl acetate (3000 mL)
  4. washwashed twice with water (2×2000 mL)
  5. extractionthe water phases were extracted with ethyl acetate (2×1500 mL)
  6. dry with materialdried with MgSO4
  7. customthe volatiles removed in vacuo
  8. filtrationThe residue was purified by filtration through silica (500 g) with ethyl acetate
  9. customThe solvent was removed
  10. customthe residue was triturated with diethyl ether
  11. customto give
  12. dry with materialafter drying in vacuo the title compound (45.6 g) as a grayish solid

Sources & evidence

ORD record
ord-f2b18bed8ff445ee851f2b3fd92cc0a7
Source dataset
uspto-grants-2012_07
Patent number
US08227491B2

Reaction notes

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