Hydrochloric Acid → Methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-hydroxypyridine-2-carboxylate

HRID 1040342Notes

Reaction equation

HRID 1040342 reaction equation
Br[C:2]1[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:12].[CH2:13]([O:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][C:26]=1[Cl:27])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C=O)C.CCOCC.CCOC(C)=O.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>[CH2:13]([O:20][C:21]1[CH:22]=[C:23]([C:2]2[N:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=2[OH:12])[CH:24]=[CH:25][C:26]=1[Cl:27])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 10796Cesium carbonateHCID 15281236Methyl 6-bromo-5-hydroxy-2-pyridinecarboxylateHCID 23005378(3-(Benzyloxy)-4-chlorophenyl)boronic acid

Product 1

HCID 66720969Methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-hydroxypyridine-2-carboxylate

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolventHCID 21584169Diethylether ethylacetateSolvent

Conditions

Temperature
90 °C

Procedure

Stir a solution of 37 g (163 mmol) of methyl 6-bromo-5-hydroxy-2-pyridine carboxylate and 51 g (196 mmol) of [3-(benzyloxy)-4-chlorophenyl]boronic acid in 300 mL of anhydrous DMF for 15 min while bubbling with argon, then add 63.8 g (196 mmol) of anhydrous caesium carbonate and 5 g (4.33 mmol) of Pd(PPh3)4. Stir the reaction mixture for 10 h at 90° C. under argon, cool to RT, then distribute in 1 L of ether/EtOAc 1:1 mixture and 1 L of a 0.5N aqueous HCl solution. Extract the aqueous phase again with 500 mL of EtOAc/ether 1:1 mixture. Combine the organic phases and wash with 4×500 mL of water. After drying over Na2SO4 and concentration under reduced pressure, take up the precipitate with 500 mL of a 7:3 mixture of pentane/DCM, filter and wash with pentane. We thus obtain 32 g of methyl 6-[3-(benzyloxy)-4-chlorophenyl]-5-hydroxypyridine-2-carboxylate in the form of yellow ochre powder.

Workup

  1. customwhile bubbling with argon
  2. temperaturecool to RT
  3. extractionExtract the aqueous phase again with 500 mL of EtOAc/ether 1:1 mixture
  4. washwash with 4×500 mL of water
  5. dry with materialAfter drying over Na2SO4 and concentration under reduced pressure
  6. additionwith 500 mL of a 7:3 mixture of pentane/DCM
  7. filtrationfilter
  8. washwash with pentane

Sources & evidence

ORD record
ord-d0ed9466d927439baa318738eb11ce75
Source dataset
uspto-grants-2013_10
Patent number
US08552201B2

Reaction notes

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