Methanol → HCID 59894515, compound

HRID 2204228Notes

Reaction equation

HRID 2204228 reaction equation
BrC1N=C(C)[C:5]([O:9][CH3:10])=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([N:42]([CH2:45][CH3:46])[CH2:43][CH3:44])C.[CH3:47][OH:48].[C]=[O:50]>C(O[Pd]OC(=O)C)(=O)C.CN(C)C=O>[CH3:10][O:9][C:5]1[CH:4]=[CH:3][C:45]([C:46]([O:48][CH3:47])=[O:50])=[N:42][C:43]=1[CH3:44]

Participants

8

Reactant 5

HCID 887MethanolHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 714064526-Bromo-3-methoxy-2-methylpyridineHCID 178418416HCID 178418416, compound

Product 1

HCID 59894515HCID 59894515, compoundYield 88.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A pressure vessel charged with 6-bromo-3-methoxy-2-methyl-pyridine (3.12 g, 15.44 mmol), diacetoxypalladium (346.6 mg, 1.54 mmol), 3-diphenylphosphanylpropyl-diphenyl-phosphane (656.5 mg, 1.54 mmol), triethylamine (6.89 mL, 49.41 mmol) and N,N-dimethyl formamide (42 mL) was treated with methanol (32.53 mL, 802.9 mmol). The vessel was charged to 90 psi with carbon monoxide (432.5 mg, 15.44 mmol) and then vented. This operation was repeated twice. The reaction was charged to 90 psi and heated at 60° C. for 21 hours. The reaction mixture was allowed to cool to 25° C. and was vented. The solvent was evaporated under reduced pressure before ethyl acetate (200 mL) and water (100 mL) were added. The layers were separated and the aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with brine (2×50 mL), dried over sodium sulfate, filtered and concentrated. The crude product was purified by silica gel chromatography utilizing a gradient of 0-50% ethyl acetate in hexane to yield methyl 5-methoxy-6-methylpicolinate (2.47 g, 88%) as a white solid. 1H NMR (400 MHz, DMSO) δ 7.94 (d, J=8.5 Hz, 1H), 7.45 (d, J=8.6 Hz, 1H), 3.90 (s, 3H), 3.83 (s, 3H), 2.40 (s, 3H). ESI-MS m/z calc. 181.1, found 182.3 (M+1)+; Retention time: 0.97 minutes (3 min run).

Workup

  1. additionThe reaction was charged to 90 psi
  2. temperatureto cool to 25° C.
  3. customThe solvent was evaporated under reduced pressure before ethyl acetate (200 mL) and water (100 mL)
  4. additionwere added
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×50 mL)
  7. washThe combined organic layers were washed with brine (2×50 mL)
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe crude product was purified by silica gel chromatography

Sources & evidence

ORD record
ord-e6ffb24fcea343b194e25f77ada79a5f
Source dataset
uspto-grants-2016_06
Patent number
US09365588B2

Reaction notes

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