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

HRID 72975

반응식

HRID 72975 반응식
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]

참가 물질

7

반응물 4

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

생성물 1

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

시약·촉매·용매 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 8857Ethyl Acetate용매

반응 조건

온도
0 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-10236de4febe4584a00b5693ec8b01d3
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828996B2

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