Methanol → Methyl 2-isopropenylquinoline-6-carboxylate

HRID 2425566Notes

Reaction equation

HRID 2425566 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]([CH3:14])=[CH2:13])[CH:6]=[CH:5]2.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.[CH3:51][OH:52].CN([CH:56]=[O:57])C>C(OCC)(=O)C.C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:12]([C:7]1[CH:6]=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:51]([O:57][CH3:56])=[O:52])[CH:3]=2)[N:8]=1)([CH3:14])=[CH2:13]

Participants

8

Reactant 5

HCID 887MethanolHCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propaneHCID 666370726-Bromo-2-isopropenylquinoline

Product 1

HCID 66637151Methyl 2-isopropenylquinoline-6-carboxylateYield 82%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 21584019Toluene ethylacetateSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-2-isopropenylquinoline (200 mg, 1.45 mmol), palladium acetate (18.1 mg, 0.081 mmol), 1,3-bis(diphenylphosphino)propane (33 mg, 0.081 mmol), triethylamine (245 mg, 2.42 mmol. 0.337 ml) and methanol (1.03 g, 1.31 ml 32.2 mmol) in dry DMF (2.5 ml) was heated at 80° C. under carbon monoxide gas (balloon) overnight (15 hours). The mixture was diluted with ethyl acetate-toluene (8:1) (159 ml) and the precipitate was filtered through a pad of celite. The organic layer was washed with water (×2), brine, dried over sodium sulfate and concentrated in vacuo to give the crude product. The crude product was purified by column chromatography on silica gel (150 g) with hexane-ethyl acetate (15:1) to furnish the title compound (150 mg, 82%) as dark yellow solid. 1H NMR (270 MHz, CDCl3) δ 2.36 (3H, s), 3.99 (3H, s), 5.53-5.57 (1H, m), 5.98 (1H, s), 7.73-7.78 (1H, m), 8.08-8.31 (3H, m), 8.54-8.56 (1H, m). MS (ESI): m/z 228.21 [M+H]+.

Workup

  1. filtrationthe precipitate was filtered through a pad of celite
  2. washThe organic layer was washed with water (×2), brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customto give the crude product
  6. customThe crude product was purified by column chromatography on silica gel (150 g) with hexane-ethyl acetate (15:1)

Sources & evidence

ORD record
ord-beb13d2d47e243da84efd72f448eb746
Source dataset
uspto-grants-2011_06
Patent number
US07964732B2

Reaction notes

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