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

HRID 1405410Notes

Reaction equation

HRID 1405410 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.CCN(CC)CC.[CH3:25][O:26][CH2:27][C:28]#[CH:29]>C(OCC)(=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[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

8

Reactant 4

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

Product 1

HCID 68153367Methyl 3-fluoro-4-(3-methoxyprop-1-ynyl)benzoate

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

To methyl 4-bromo-3-fluoro-benzoate (2.50 g, 10.7 mmol), copper (I) iodide (204 mg, 1.07 mmol) and Pd(PPh3)2Cl2 (753 mg, 1.07 mmol) in a flask under Argon was added DMF (degassed for 30 min) and reaction cooled to 0 C. Et3N (1.95 mL, 14.0 mmol) was added followed by 3-methoxyprop-1-yne (997 μL, 11.8 mmol) and the mixture was allowed to stir at 60° C. for 70 min. The mixture was cooled, diluted with ethyl acetate and filtered. The filtrate was washed sequentially with 1 M HCl, 10% NH4OH and brine solutions. The organic layer was separated, dried and purified with silica gel using ethyl acetate-hexanes to give methyl 3-fluoro-4-(3-methoxyprop-1-ynyl)benzoate. 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. temperaturecooled to 0 C
  2. temperatureThe mixture was cooled
  3. filtrationfiltered
  4. washThe filtrate was washed sequentially with 1 M HCl, 10% NH4OH and brine solutions
  5. customThe organic layer was separated
  6. customdried
  7. custompurified with silica gel

Sources & evidence

ORD record
ord-bc590734a00140bc9dd9539f38c16470
Source dataset
uspto-grants-2014_12
Patent number
US08916565B2

Reaction notes

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