Methanol → Methyl 5-(2-hydroxypropan-2-yl)pyridine-3-carboxylate

HRID 1048949Notes

Reaction equation

HRID 1048949 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]([OH:11])([CH3:10])[CH3:9])[CH:5]=[N:6][CH:7]=1.CC1(C)C2[C:34](=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:33][C:15]2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C[OH:55].C(N(CC)CC)C>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[OH:11][C:8]([C:4]1[CH:3]=[C:2]([C:15]([O:33][CH3:34])=[O:55])[CH:7]=[N:6][CH:5]=1)([CH3:10])[CH3:9]

Participants

7

Reactant 4

HCID 887MethanolHCID 8471TriethylamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 223919662-(5-Bromo-3-pyridyl)propan-2-ol

Product 1

HCID 66684512Methyl 5-(2-hydroxypropan-2-yl)pyridine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of the title compound from Step A (1.99 g, 9.21 mmol), palladium acetate (0.041 g, 0.041 Xantphos (0.213 g, 0.368 mmol), methanol (3.73 mL, 92.1 mmol), and triethylamine (18.33 mL, 132.0 mmol) was stirred under an atmosphere of carbon monoxide at 70° C. overnight. The reaction was then cooled to room temperature, diluted with ethyl acetate, filtered through CELITE© and concentrated under reduced pressure. Purification by flash chromatography on silica gel (30% ethyl acetate in hexanes) provided the title compound: LCMS m/z 195.99 [M+H]+; 1H NMR (500 MHz, CDCl3) δ 9.09 (d, J=1.8 Hz, 1 H), 8.92 (d, J=2.2 Hz, 1 H), 8.41 (t, J=2.0 Hz, 1 H), 3.96 (s, 3 H), 2.27 (br s, 1 H), 1.64 (s, 6 H).

Workup

  1. temperatureThe reaction was then cooled to room temperature
  2. filtrationfiltered through CELITE©
  3. concentrationconcentrated under reduced pressure
  4. customPurification by flash chromatography on silica gel (30% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-03fa3b37ed0f432a8b91e2151d60ddb4
Source dataset
uspto-grants-2016_07
Patent number
US09382226B2

Reaction notes

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