Dimethylformamide → Methyl 3-fluoro-4-(3-methoxyprop-1-ynyl)benzoate

HRID 713060Notes

Reaction equation

HRID 713060 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[F:12].CN(C=O)C.C(N(CC)CC)C.[CH3:25][O:26][CH2:27][C:28]#[CH:29]>CCOC(C)=O.[Cu]I>[F:12][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:2]=1[C:29]#[C:28][CH2:27][O:26][CH3:25])[C:6]([O:8][CH3:9])=[O:7]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 693933-MethoxypropyneHCID 21951878Methyl 4-bromo-3-fluorobenzoate

Product 1

HCID 68153367Methyl 3-fluoro-4-(3-methoxyprop-1-ynyl)benzoateYield 61%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of methyl 4-bromo-3-fluoro-benzoate (2.5 g, 10.7 mmol) and copper (I) iodide (204 mg, 1.07 mmol) and palladium dichlorobis(triphenylphosphine) complex (753 mg, 1.07 mmol) under an atmosphere of argon was added DMF (21 mL) and the reaction mixture was cooled to 0° C. Triethylamine (1.95 mL, 13.9 mmol) was added followed by 3-methoxyprop-1-yne (997 μL, 11.8 mmol) and the reaction mixture was stirred at 60° C. for 70 minutes. The reaction mixture was cooled, diluted with EtOAc and filtered over Celite®. The filtrate was washed sequentially with 1 M HCl, 10% NH4OH and brine. The organic layer was separated, dried and concentrated in vacuo and the resulting residue was purified by silica gel column chromatography using EtOAc-hexanes (10-100%) as eluent to give methyl 3-fluoro-4-(3-methoxyprop-1-ynyl)benzoate (1.45 g, 61%). ESI-MS m/z calc. 222.2. found 223.2 (M+1)+; Retention time: 1.53 minutes (3 min run); 1H NMR (400 MHz, CDCl3) δ 7.75 (ddd, J=11.2, 8.8, 1.5 Hz, 2H), 7.50 (dd, J=7.9, 7.0 Hz, 1H), 4.37 (s, 2H), 3.92 (s, 3H), 3.47 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered over Celite®
  3. washThe filtrate was washed sequentially with 1 M HCl, 10% NH4OH and brine
  4. customThe organic layer was separated
  5. customdried
  6. concentrationconcentrated in vacuo
  7. customthe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0ddcfe1b8c4147b4966c4a94041f672a
Source dataset
uspto-grants-2015_11
Patent number
US09181273B2

Reaction notes

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