Trifluoroacetic acid → 4-((2,2,2-Trifluoroethyl)amino)-2-(trifluoromethyl)benzonitrile

HRID 1173397ノート

反応式

HRID 1173397 の反応式
[NH2:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1.[BH3-]C#N.[Na+].[C:18](O)([C:20]([F:23])([F:22])[F:21])=O.[H][H].O.FC(F)(F)C=O.C([O-])(O)=O.[Na+]>C(Cl)Cl>[F:21][C:20]([F:23])([F:22])[CH2:18][NH:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([C:10]([F:11])([F:12])[F:13])[CH:3]=1

参加物

8

反応物 6

HCID 6422Trifluoroacetic acidHCID 516892Sodium Bicarbonate2 回HCID 5221704-Amino-2-(trifluoromethyl)benzonitrileHCID 27813662,2,2-Trifluoroacetaldehyde hydrateHCID 5003444Sodium cyanoborohydrideHCID 178418361HCID 178418361、化合物

生成物 1

HCID 431385374-((2,2,2-Trifluoroethyl)amino)-2-(trifluoromethyl)benzonitrile収率 75.1%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

To a slurry of 4-amino-2-(trifluoromethyl)benzonitrile (30.09 g, 162 mmol) and NaBH3CN (21.35 g, 340 mmol) in CH2Cl2 (160 mL) at ice bath temperature neat TFA (160 mL, 2.08 mol) was added dropwise at a rate such that the internal temperature remained below 5° C. (CAUTION: exothermic reaction with hydrogen gas evolution). Trifluoroacetaldehyde hydrate (52.2 g, 405 mmol) was then added over 5 min (CAUTION: slightly exothermic reaction, with gas evolution). After 41 h, the mixture was slowly poured into sat'd NaHCO3 (1 L) at 0° C. The mixture was then completely neutralized by portionwise addition of solid NaHCO3. The mixture was stirred 30 min and precipitated solids were collected by filtration. Organic and aqueous phases of the filtrate were separated, and the aqueous layer extracted with CH2Cl2 (3×150 mL). Combined organic extracts were concentrated to dryness, combined with the solids collected previously, dissolved in EtOAc, washed (H2O, brine), dried over Na2SO4, filtered through a short pad of Celite and concentrated to dryness. Recrystallization from EtOAc/hexanes yielded 32.61 g of the title compound as slightly tan crystalline plates, mp 132.5-134° C.: 1H NMR (300 MHz, CD3OD) δ 7.59 (d, J=8.8 Hz, 1H), 7.05 (d, J=2.2 Hz, 1H), 6.92 (dd, J=8.7, 2.4 Hz, 1H), 3.92 (q, J=9.2 Hz, 2H).

後処理

  1. customremained below 5° C.
  2. customslightly exothermic reaction
  3. customprecipitated solids
  4. filtrationwere collected by filtration
  5. customOrganic and aqueous phases of the filtrate were separated
  6. extractionthe aqueous layer extracted with CH2Cl2 (3×150 mL)
  7. concentrationCombined organic extracts were concentrated to dryness
  8. customcollected previously
  9. dissolutiondissolved in EtOAc
  10. washwashed (H2O, brine)
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered through a short pad of Celite
  13. concentrationconcentrated to dryness
  14. customRecrystallization from EtOAc/hexanes

出典と根拠

ORDレコード
ord-b06de642a42046c8ac10dea2a3866554
出典データセット
uspto-grants-2010_11
特許番号
US07834063B2

反応ノート

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