Isopropyl iodide → 3-Fluoro-4-isopropoxy-5-methoxybenzaldehyde

HRID 72952

반응식

HRID 72952 반응식
[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:11][CH3:12])[C:9]=1[OH:10])[CH:5]=[O:6].C(=O)([O-])[O-].[K+].[K+].I[CH:20]([CH3:22])[CH3:21]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([CH:7]=[C:8]([O:11][CH3:12])[C:9]=1[O:10][CH:20]([CH3:22])[CH3:21])[CH:5]=[O:6]

참가 물질

5

반응물 3

HCID 6362Isopropyl iodideHCID 11430Potassium CarbonateHCID 5984523-Fluoro-4-hydroxy-5-methoxybenzaldehyde

생성물 1

HCID 866724743-Fluoro-4-isopropoxy-5-methoxybenzaldehyde

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A solution of 3-fluoro-4-hydroxy-5-methoxy-benzaldehyde (250 mg, 1.5 mmol) in DMF (2.5 mL) was treated with potassium carbonate (812 mg, 5.9 mmol) and stirred for 30 minutes. 2-Iodopropane (500 mg, 2.9 mmol) was added over 10 minutes and reaction mixture was stirred for 20 hours. The reaction mixture was partitioned between EtOAc and saturated aqueous sodium chloride solution. The organic layer was washed with saturated sodium bicarbonate solution. The organic layer was separated and dried over sodium sulfate, filtered and concentrated in vacuo to give 3-fluoro-4-isopropoxy-5-methoxybenzaldehyde. To the aldehyde was added tert-butanol (6.7 mL) and 2-methylbut-2-ene (4 mL, 38.2 mmol) and the reaction mixture was cooled to 0° C. A solution of chlorite (345 mg, 3.8 mmol) and sodium dihydrogen phosphate hydrate (527 mg, 3.8 mmol) in water (6.7 mL) was added dropwise over 5 minutes, and the reaction mixture was stirred 30 minutes. The reaction mixture was warmed to room temperature and stirred for 12 hours. The reaction mixture was basified with 1 N NaOH solution and extracted with ethyl acetate (2×50 mL). The aqueous layer was acidified with 1 N HCl solution and extracted with EtOAc (4×50 mL). The combined organics were dried (Na2SO4), filtered, and concentrated in vacuo to afford 3-fluoro-4-isopropoxy-5-methoxy-benzoic acid (190 mg, 56%) as a white solid. ESI-MS m/z calc. 228.0. Found 229.3 (M−1)+; Retention time: 1.57 minutes (3 min run).

후처리

  1. customreaction mixture
  2. stirringwas stirred for 20 hours
  3. customThe reaction mixture was partitioned between EtOAc and saturated aqueous sodium chloride solution
  4. washThe organic layer was washed with saturated sodium bicarbonate solution
  5. customThe organic layer was separated
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-47f6222404fb44d1820c1074499d63c3
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08828996B2

연결된 노트

불러오는 중…