Methane → N-[4-(Phenylcarbonyl)phenyl]-3,3,-difluoro-2-hydroxy-2-methylpropanamide

HRID 865249

反応式

HRID 865249 の反応式
[OH:1][C:2]([CH:7]([F:9])[F:8])([CH3:6])[C:3](O)=[O:4].S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:28]=[CH:27][C:18]([C:19]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:20])=[CH:17][CH:16]=1.Cl.C>CC(N(C)C)=O>[C:21]1([C:19]([C:18]2[CH:17]=[CH:16][C:15]([NH:14][C:3](=[O:4])[C:2]([OH:1])([CH3:6])[CH:7]([F:9])[F:8])=[CH:28][CH:27]=2)=[O:20])[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

参加物

7

反応物 5

HCID 297MethaneHCID 313Hydrochloric AcidHCID 143464-AminobenzophenoneHCID 24386Thionyl ChlorideHCID 147860322-(Difluoromethyl)-2-hydroxypropionic acid

生成物 1

HCID 21480151N-[4-(Phenylcarbonyl)phenyl]-3,3,-difluoro-2-hydroxy-2-methylpropanamide

試薬・触媒・溶媒 1

HCID 31374Dimethylacetamide溶媒

反応条件

温度
-10 °C

実験手順

A solution of 2-hydroxy-2-difluoromethylpropionic acid (1.07 g, 7.65 mmol) in dry dimethylacetamide (15 ml) was stirred under a nitrogen atmosphere at -10° C. Thionyl chloride (0.91 g, 7.65 mmol). was added and the resulting mixture was allowed to stir at -10° C. for 1 hour. 4-Aminobenzophenone (1.0 g, 5.1 mmol) was then added and the reaction mixture was stirred at -10° C. for a further 15 mins. The solution was then allowed to warm to room temperature where it was stirred overnight. The reaction mixture was poured into hydrochloric acid solution (1M) and extracted with ethyl acetate. The combined ethyl acetate fractions were washed with water and brine. After drying (Na2SO4) and decolorizarion (Charcoal) the solution was evaporated in vacuo. A off-white foam was obtained which was triturated with hexane/ethyl acetate. The crude product was filtered through a short silica gel column with chloroform and crystallized from chloroform/hexane to give the title tertiary carbinol (0.89 g, 5%) as shiny, buff-colered crystals; mp=123°-124° C. 1H-NMR (300 MHz, d6 -DMSO): 1.45 (s, 3H, CH3), 6.17 (t, J=55 Hz, 1H, CHF2), 6.77 (s, 1H, OH), 7.56 (t, 2H, ArH), 7.65-7.76 (m, 5H, ArH), 7.96 (d, J=8.7 Hz, 2H, ArH), 10.19 (s, 1H, NH). MS (CI, CH4): 320(M+1, 100).

後処理

  1. additionwas added
  2. stirringthe reaction mixture was stirred at -10° C. for a further 15 mins
  3. temperatureto warm to room temperature where it
  4. stirringwas stirred overnight
  5. extractionextracted with ethyl acetate
  6. washThe combined ethyl acetate fractions were washed with water and brine
  7. dry with materialAfter drying (Na2SO4) and decolorizarion (Charcoal) the solution
  8. customwas evaporated in vacuo
  9. customA off-white foam was obtained which
  10. customwas triturated with hexane/ethyl acetate
  11. filtrationThe crude product was filtered through a short silica gel column with chloroform
  12. customcrystallized from chloroform/hexane
  13. customto give the title tertiary carbinol (0.89 g, 5%) as shiny, buff-colered crystals

出典と根拠

ORDレコード
ord-e963a83698a846d7b4e7f4de2b83a083
出典データセット
uspto-grants-1996_10
特許番号
US05565477

関連ノート

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