Sodium Carbonate → tert-butyl 4-[2-fluoro-3-(hydroxymethyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate

HRID 1021215Notes

Reaction equation

HRID 1021215 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[F:7][C:8]1[C:13]([CH:14]=[O:15])=[CH:12][CH:11]=[CH:10][C:9]=1B(O)O.FC(F)(F)S(O[C:25]1[CH2:26][CH2:27][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:29][CH:30]=1)(=O)=O.[BH4-].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCO.O.C1(C)C=CC=CC=1>[F:7][C:8]1[C:13]([CH2:14][OH:15])=[CH:12][CH:11]=[CH:10][C:9]=1[C:25]1[CH2:30][CH2:29][N:28]([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:27][CH:26]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 4311764Sodium borohydrideHCID 10991161Tert-butyl 4-(trifluoromethanesulfonyloxy)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 162178292-Fluoro-3-formylphenylboronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 86686194tert-butyl 4-[2-fluoro-3-(hydroxymethyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylateYield 68.7%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent2×HCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

Under argon atmosphere, sodium carbonate (1000 mg) and tetrakis(triphenylphosphine)palladium (170 mg) were added to a mixture of (2-fluoro-3-formylphenyl)boronic acid (700 mg), tert-butyl 4-{[(trifluoromethyl)sulfonyl]oxy}-3,6-dihydropyridine-1(2H)-carboxylate (1000 mg), toluene (15 ml), EtOH (5 ml) and water (5 ml) followed by stirring at 80° C. overnight. The reaction mixture was concentrated under reduced pressure, and CHCl3 and a saturated aqueous sodium hydrogen carbonate solution were then added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc). The purified product thus obtained was mixed with EtOH, and NaBH4 (120 mg) was added thereto, followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and then EtOAc and water were added thereto. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/EtOAc) to obtain tert-butyl 4-[2-fluoro-3-(hydroxymethyl)phenyl]-3,6-dihydropyridine-1(2H)-carboxylate (637 mg).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, and CHCl3
  2. additiona saturated aqueous sodium hydrogen carbonate solution were then added
  3. dry with materialThe organic layer was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)
  6. customThe purified product thus obtained
  7. additionwas added
  8. stirringby stirring at room temperature for 30 minutes
  9. concentrationThe reaction mixture was concentrated under reduced pressure
  10. additionEtOAc and water were added
  11. dry with materialThe organic layer was dried over Na2SO4
  12. concentrationconcentrated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography (hexane/EtOAc)

Sources & evidence

ORD record
ord-36ecc3a2412f4b4ebc0ec6f538d7cdc6
Source dataset
uspto-grants-2014_05
Patent number
US08716470B2

Reaction notes

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