Sodium Carbonate → 2-Formyl-6-naphthylpyridine

HRID 599119Notes

Reaction equation

HRID 599119 reaction equation
[C:1]1(B(O)O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.C([O-])([O-])=O.[Na+].[Na+].Br[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([CH:27]=[O:28])[N:22]=1>C1(C)C=CC=CC=1.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>[CH:27]([C:23]1[CH:24]=[CH:25][CH:26]=[C:21]([C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)[N:22]=1)=[O:28]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2545321-Naphthaleneboronic acidHCID 27570096-Bromopyridine-2-carbaldehyde

Product 1

HCID 120705612-Formyl-6-naphthylpyridineYield 87%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
70 °C

Procedure

Inside of a dry box, naphthylboronic acid (9.12 g, 53.0 mmol) and Na2CO3 (11.64 g, 110 mmol) are dissolved in 290 mL of degassed 4:1 H2O/MeOH. This solution is added to a solution of 8 g (43 mmol) of 2-bromo-6-formylpyridine and 810 mg (0.7 mmol) of Pd(PPh3)4 in 290 mL of degassed toluene. The charged reactor is removed from the dry box, while under a blanket of N2 and is connected to the house N2 line. The biphasic solution is vigorously stirred and heated to 70° C. for 4 h. On cooling to RT, the organic phase is separated. The aqueous layer is washed with 3×75 mL of Et2O. The combined organic extracts are washed with 3×100 mL of H2O and 1×100 mL of brine and dried over Na2SO4. After removing the volatiles in vacuo, the resultant light yellow oil is purified via trituration with hexanes. The isolated material is recrystallized from a hot hexane solution and ultimately yielded 8.75 g, 87% yield. mp 65-66° C.

Workup

  1. customof degassed 4:1 H2O/MeOH
  2. customThe charged reactor is removed from the dry box, while under a blanket of N2
  3. temperatureOn cooling to RT
  4. customthe organic phase is separated
  5. washThe aqueous layer is washed with 3×75 mL of Et2O
  6. washThe combined organic extracts are washed with 3×100 mL of H2O and 1×100 mL of brine
  7. dry with materialdried over Na2SO4
  8. customAfter removing the volatiles in vacuo
  9. customthe resultant light yellow oil is purified via trituration with hexanes
  10. customThe isolated material is recrystallized from a hot hexane solution and ultimately yielded 8.75 g, 87% yield

Sources & evidence

ORD record
ord-0246218092be4f60bd89f8f907ce889c
Source dataset
uspto-grants-2011_03
Patent number
US07897679B2

Reaction notes

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