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

HRID 72975

反応式

HRID 72975 の反応式
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]

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
0 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-10236de4febe4584a00b5693ec8b01d3
出典データセット
uspto-grants-2014_09
特許番号
US08828996B2

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