Thionyl Chloride → N-[4-(2-Pyridylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamide

HRID 865276노트

반응식

HRID 865276 반응식
[F:1][CH:2]([F:11])[C:3]([CH:8]([F:10])[F:9])([OH:7])[C:4](O)=[O:5].S(Cl)(Cl)=O.[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([C:25]1[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=1)(=[O:24])=[O:23].C(=O)(O)[O-].[Na+]>CC(N(C)C)=O.O>[N:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[S:22]([C:25]1[CH:31]=[CH:30][C:28]([NH:29][C:4](=[O:5])[C:3]([OH:7])([CH:8]([F:10])[F:9])[CH:2]([F:11])[F:1])=[CH:27][CH:26]=1)(=[O:23])=[O:24]

참가 물질

7

반응물 4

HCID 24386Thionyl ChlorideHCID 516892Sodium BicarbonateHCID 105138504-(2-Pyridylsulfonyl)anilineHCID 222874542,2-Bis-difluoromethyl-2-hydroxyacetic acid

생성물 1

HCID 21480114N-[4-(2-Pyridylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamide수율 43%

시약·촉매·용매 2

HCID 962Water용매HCID 31374Dimethylacetamide용매

반응 조건

온도
-10 °C

실험 절차

To a solution of 2,2-bis-difluoromethyl-2-hydroxyacetic acid (0.5 g, 2.84 mmole) in dimethylacetamide (10 ml) at -10° C. was added thionyl chloride (0.34 g, 2.84 mmol) dropwise. The resulting solution was stirred at -10° C. for approximately 30 min. 4-(2-Pyridylsulfonyl)aniline (0.58 g, 2.5 mmol) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into water, and sodium bicarbonate solution was added to give a pH of 7-7.5. A brown colored precipitate was formed. The solid was filtered, washed with water, and dried. Crystallization and decoloration (charcoal) from ethyl acetate/methanol/hexane gave the title compound (0.42 g, 43%) as off-white leaves; mp 200°-202° C. 1H-NMR(300 HHz, d6 -DMSO): 6.45 (t, J=54.09 Hz, 2H, HCF2), 7.68(t, J=6.24 Hz, 1H, ArH), 7.92-8.03 (m, 5H, ArH, OH), 8.11-8.21 (m, 2H, ArH), 8.68 (d, J=4.47Hz, 1H, ArH), 10.54 (s, 1H, NH). MS(CI,CH4): 393 (M+100%).

후처리

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. additionwas added
  3. customto give a pH of 7-7.5
  4. customA brown colored precipitate was formed
  5. filtrationThe solid was filtered
  6. washwashed with water
  7. customdried
  8. customCrystallization and decoloration (charcoal) from ethyl acetate/methanol/hexane

출처 및 근거

ORD 기록
ord-a1c6af4ca5d541a6b90ae0eb4038baf0
출처 데이터셋
uspto-grants-1996_10
특허 번호
US05565477

반응 노트

불러오는 중…