Triethylamine → 4-(4-Fluoro-3-methoxy-benzylcarbamoyl)-benzenesulfonyl chloride

HRID 737016노트

반응식

HRID 737016 반응식
[Cl:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9](Cl)=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3].[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH2:20])=[CH:17][C:16]=1[O:23][CH3:24].CCN(CC)CC>C1COCC1.CN(C1C=CN=CC=1)C>[F:14][C:15]1[CH:22]=[CH:21][C:18]([CH2:19][NH:20][C:9]([C:8]2[CH:12]=[CH:13][C:5]([S:2]([Cl:1])(=[O:4])=[O:3])=[CH:6][CH:7]=2)=[O:10])=[CH:17][C:16]=1[O:23][CH3:24]

참가 물질

6

반응물 3

HCID 8471TriethylamineHCID 820244-(Chlorosulphonyl)benzoyl chlorideHCID 442031244-Fluoro-3-methoxybenzylamine

생성물 1

HCID 589751944-(4-Fluoro-3-methoxy-benzylcarbamoyl)-benzenesulfonyl chloride수율 30.9%

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 8028Tetrahydrofuran용매2회

반응 조건

온도
-78 °C

실험 절차

Dissolve 4-chlorosulfonyl-benzoyl chloride (3.18 g, 13.3 mmol) in THF (25 mL) and cool to −78° C. Slowly add a pre-mixed solution of 4-fluoro-3-methoxybenzyl-amine (1.91 g, 12.3 mmol), Et3N (1.64 mL, 11.8 mmol), and DMAP (150 mg, 1.23 mmol) in THF (25 mL) to the above cooled solution over 1 h. Stir the resulting mixture at −78° C. for 1 h, then warm to RT and stir for 4 h. Remove all solids by filtration and wash with THF (5 mL). Concentrate the filtrate and re-dissolve the crude material in EtOAc (30 mL) and wash with 1N HCl (30 mL). Separate the organic and aqueous layers and extract the aqueous phase with additional EtOAc (30 mL). Combine the organic solutions dry, filter, and concentrate. Purify the crude material by flash chromatography, using a linear gradient of 100% hexanes to 40% EtOAc/hexanes) to give the title compound as a white solid (1.36 g, 28%). MS (ES−) 356.1 (M−1)−. 1H NMR (400 MHz, CDCl3): δ 8.11 (d, 2H, J=8.3), 8.00 (d, 2H, J=8.8), 7.05 (dd, 1H, J=8.2, 11.1), 6.96 (dd, 1H, J=1.9, 8.0), 6.86 (m, 1H), 6.44 (br s, 1H), 4.61 (d, 2H, J=5.7), 3.88 (s, 3H).

후처리

  1. temperaturewarm to RT
  2. stirringstir for 4 h
  3. customRemove all solids
  4. filtrationby filtration
  5. washwash with THF (5 mL)
  6. concentrationConcentrate the filtrate
  7. dissolutionre-dissolve the crude material in EtOAc (30 mL)
  8. washwash with 1N HCl (30 mL)
  9. customSeparate the organic and aqueous layers
  10. extractionextract the aqueous phase with additional EtOAc (30 mL)
  11. customCombine the organic solutions dry
  12. filtrationfilter
  13. concentrationconcentrate
  14. customPurify the crude material by flash chromatography

출처 및 근거

ORD 기록
ord-069298082eef4447995ede85896939bd
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07595339B2

반응 노트

불러오는 중…