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

HRID 2259705ノート

反応式

HRID 2259705 の反応式
[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.[C:16]1([S:22]([C:25]2[CH:31]=[CH:30][C:28]([NH2:29])=[CH:27][CH:26]=2)(=[O:24])=[O:23])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.C(=O)(O)[O-].[Na+]>CC(N(C)C)=O.O>[C:16]1([S:22]([C:25]2[CH:26]=[CH:27][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:30][CH:31]=2)(=[O:23])=[O:24])[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1

参加物

7

反応物 4

HCID 24386Thionyl ChlorideHCID 5166664-(Phenylsulfonyl)anilineHCID 516892Sodium BicarbonateHCID 222874542,2-Bis-difluoromethyl-2-hydroxyacetic acid

生成物 1

HCID 21480121N-[4-(Phenylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamide収率 57.2%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 31374Dimethylacetamide溶媒

反応条件

温度
-10 °C

実験手順

To a solution of 2,2-bis-difluoromethyl-2-hydroxyacetic acid (0.5 g, 2.84 mmoles) in dimethylacetamide (10 ml) at -10° C. was added thionyl chloride (0.34 g, 2.84 mmoles) dropwise. The resulting solution was stirred at -10° C. for approximately 30 mins. 4-(Phenylsulfonyl) aniline (0.58 g, 2.5 mmoles) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into water, sodium bicarbonate solution added to give a pH of 7 and extracted with ethyl acetate. The ethyl acetate extracts were combined, washed with water, brine, dried (Na2SO4), decolorized (charcoal), and evaporated. The crude solid was dissolved in ether, clarified by filtration, and evaporated. Crystallization from methanol/water gave the title compound (0.56 g, 57%) as white, silky needles; mp 105°-108° C. 1H-NMR (300 MHz, d6 -DMSO) 6.44 (t, J=53.94 Hz, 2H, HCF2), 7.58-7.68(m, 3H, ArH), 7.92-8.01 (m, 7H, ArH, OH), 10.51 (s, 1H, NH). MS(CI,CH4): 392 (M+1, 100%). Analysis for C16H13F4NO4S: Calculated: C, 49.11; H, 3.35; N, 3.58. Found: C, 49.15; H, 3.48; N, 3.54

後処理

  1. stirringthe reaction mixture was stirred overnight at room temperature
  2. additionadded
  3. customto give a pH of 7
  4. extractionextracted with ethyl acetate
  5. washwashed with water, brine
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. dissolutionThe crude solid was dissolved in ether
  9. filtrationclarified by filtration
  10. customevaporated
  11. customCrystallization from methanol/water

出典と根拠

ORDレコード
ord-996cd9a182b14741984974c9ab5aa7ef
出典データセット
uspto-grants-1995_12
特許番号
US05474999

反応ノート

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