Acetovanillone → HCID 67245487, compound

HRID 2422859Notes

Reaction equation

HRID 2422859 reaction equation
[CH3:1][C:2]([C:4]1[CH:12]=[CH:11][C:9](O)=[C:6]([O:7][CH3:8])[CH:5]=1)=[O:3].C1C=CC(N(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].[CH3:40][O:41][C:42]1[C:47](B(O)O)=[CH:46][CH:45]=[CH:44][N:43]=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.CN1CCCC1=O.O1CCCC1>[CH3:8][O:7][C:6]1[CH:5]=[C:4]([C:2](=[O:3])[CH3:1])[CH:12]=[CH:11][C:9]=1[C:47]1[C:42]([O:41][CH3:40])=[N:43][CH:44]=[CH:45][CH:46]=1

Participants

8

Reactant 4

HCID 2214AcetovanilloneHCID 11430Potassium CarbonateHCID 142176Phenyl triflimideHCID 2762709(2-Methoxypyridin-3-yl)boronic acid

Product 1

HCID 67245487HCID 67245487, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of acetovanillone (0.332 g, 2.0 mmol), N-phenyl-bis(trifluoromethane-sulfonimide) (710 mg, 2.0 mmol), potassium carbonate (830 mg, 6.0 mmol) and tetrahydrofuran (3.0 ml) was heated to 120° C. for 6 min in a microwave oven. 2-Methoxypyridine-3-boronic acid (611 mg, 4 mmol), tetrakis(triphenylphosphine)palladium (0) (115 mg, 100 μmol), N-methylpyrrolidinone (1 ml) were then added and the mixture heated in the microwave at 120° C. for 10 min. The reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic phase was separated and washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate and the solvent evaporated to give 1-[3-methoxy-4-(2-methoxy-pyridin-3yl)-phenyl]-ethanone in quantitative yield. Reductive amination with ammonium acetate (20 equivalents) in methanol (50 ml) containing sodium cyanoborohydride (1 equivalent) followed by aqueous work-up with saturated aqueous sodium bicarbonate and extraction into ethyl actetate gave, after solvent was evaporated 1-[3-methoxy-4-(2-methoxy-pyridin-3yl)-phenyl]-ethylamine. To 1-[3-methoxy-4-(2-methoxy-pyridin-3yl)-phenyl]-ethylamine was added 2-trifluoromethoxy-benzenesulfonyl chloride (1 equivalent) in dichloromethane, diisopropylethylamine (4 equivalents) and the mixture overnight. The racemic product was isolated by normal phase HPLC on silica gel eluting with heptane/ethyl acetate and the solvent evaporated to give a clear oily solid (72 mg). 1H NMR (400 MHz, CDCl3): δ 8.15 (d, 1H), 7.9 (d, 1H), 7.5 (m, 1H), 7.4 (m, 1H), 7.3-7.2 (m, 2H), 7.05 (d, 1H), 6.9 (m, 1H), 6.75-6.65 (m, 2H), 5.0 (d, 1H), 4.55 (m, 1H), 3.91 (s, 3H), 3.67 (s, 3H), 1.51 (d, 3H) ppm; MS (ESI) m/z: 483.3 [M+1]+. The racemate was resolved by chiral HPLC (CHIRALPAK-AS, eluting with 9:1 isohexane/ethanol) to give the title compound (11 mg) and its enantiomer (11) mg.

Workup

  1. temperaturethe mixture heated in the microwave at 120° C. for 10 min
  2. customThe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution
  3. customThe organic phase was separated
  4. washwashed with saturated aqueous sodium bicarbonate solution
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent evaporated

Sources & evidence

ORD record
ord-504aad128b3e4fbf94576256098c41d6
Source dataset
uspto-grants-2011_06
Patent number
US07960365B2

Reaction notes

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