Sodium Carbonate → benzyl 4-(4-hydroxyphenyl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 1675101Notes

Reaction equation

HRID 1675101 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].FC(F)(F)S(O[C:13]1[CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[O:20])[CH2:15][CH:14]=1)(=O)=O.[OH:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1>O1CCOCC1.O.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:31][C:32]1[CH:37]=[CH:36][C:35]([C:13]2[CH2:18][CH2:17][N:16]([C:19]([O:21][CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[CH2:15][CH:14]=2)=[CH:34][CH:33]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343604-Hydroxyphenylboronic acidHCID 11303044benzyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 66788302benzyl 4-(4-hydroxyphenyl)-5,6-dihydropyridine-1(2H)-carboxylateYield 66.4%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

Sodium carbonate (96 g, 909.79 mmol) was added to benzyl 4-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (123.1 g, 303.26 mmol) and 4-hydroxyphenylboronic acid (46.0 g, 333.59 mmol) in a mixture of dioxane (1000 mL) and water (250 mL). The resulting mixture was bubbled with nitrogen for 10 minutes then 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (5.49 g, 7.58 mmol) was added and the reaction mixture was heated at 80° C. for 1 hour, then cooled to room temperature. The reaction mixture was diluted with DCM (2 L) and washed with water (2 L). The aqueous washing was re-extracted with DCM (1 L), then the combined organics were washed with saturated brine (500 mL), dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 10 to 30% EtOAc in isohexane. Fractions containing the desired product were evaporated to dryness then triturated with isohexane, filtered and dried to afford benzyl 4-(4-hydroxyphenyl)-5,6-dihydropyridine-1(2H)-carboxylate (62.3 g, 66.4%) as a solid.

Workup

  1. customThe resulting mixture was bubbled with nitrogen for 10 minutes
  2. temperaturecooled to room temperature
  3. washwashed with water (2 L)
  4. washThe aqueous washing
  5. extractionwas re-extracted with DCM (1 L)
  6. washthe combined organics were washed with saturated brine (500 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customto afford crude product
  11. customThe crude product was purified by flash silica chromatography, elution gradient 10 to 30% EtOAc in isohexane
  12. additionFractions containing the desired product
  13. customwere evaporated to dryness
  14. customthen triturated with isohexane
  15. filtrationfiltered
  16. customdried

Sources & evidence

ORD record
ord-9e222db6d6b34642ad6bddd6fb044cb7
Source dataset
uspto-grants-2011_08
Patent number
US08003649B2

Reaction notes

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