Hydrochloric Acid → HCID 53846384、化合物

HRID 1378617ノート

反応式

HRID 1378617 の反応式
[F:1][C:2]([F:7])([F:6])[C:3]([NH2:5])=O.P12(SP3(SP(SP(S3)(S1)=S)(=S)S2)=S)=S.Br[CH:23]([C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=1)[C:24]([C:26]1[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[CH:28][CH:27]=1)=O.Cl.[OH-].[Na+].[S:44]1C=CN=C1>C1(C)C=CC=CC=1.C(Cl)Cl>[F:40][C:37]1[CH:38]=[CH:39][C:34]([C:23]2[S:44][C:3]([C:2]([F:7])([F:6])[F:1])=[N:5][C:24]=2[C:26]2[CH:31]=[CH:30][C:29]([S:32][CH3:33])=[CH:28][CH:27]=2)=[CH:35][CH:36]=1

参加物

9

反応物 6

HCID 313Hydrochloric AcidHCID 9256ThiazoleHCID 14798Sodium HydroxideHCID 14817Phosphorus sulfide (P2S5)HCID 67717TrifluoroacetamideHCID 54373829HCID 54373829、化合物

生成物 1

HCID 53846384HCID 53846384、化合物収率 23%

試薬・触媒・溶媒 2

HCID 1140Toluene溶媒2 回HCID 6344Dichloromethane溶媒

実験手順

To a solution of trifluoroacetamide (13.7 g, 121.2 mmol) in toluene (30 mL) was added solid P4S10 (5.4 g, 12.1 mmol) and the mixture refluxed for 60 hours. The resulting orange "coarse" suspension was cooled to room temperature and the solid pulverized to form a fine suspension. One fourth of this toluene suspension (7.5 mL, ca. 30 mmol of theory) was transferred to a 25 mL round bottom flask and 2-bromo-2-(4-fluorophenyl)-1-(4-methylthiophenyl)ethanone (1.24 g, 3.66 mmol) (Example 20, Step 2) added in one portion. This suspension was heated to reflux for 1.5 hours, cooled to 50° C., and 1.0 N HCl solution (1 mL) added carefully and reflux continued for 1 hour more. This reaction was cooled to room temperature and let stand overnight. To this solution was added 2 N NaOH solution until the exotherm subsided and the reaction was stirred for 1 hour longer. The resulting black suspension was diluted with methylene chloride and washed with NaHCO3 saturated solution, dried over Na2SO4, filtered and concentrated in vacuo yielding a brown semi-solid. This crude thiazole was flash chromatographed (9:1 hexane:methylene chloride) yielding 5-(4-fluorophenyl)-4-(4-methylthiophenyl)-2-trifluoromethylthiazole (0.28 g, 23%) as yellow oil which slowly solidified mp: 59°-60° C.; 1HNMR (CDCl3) 300 mHz 7.43 (d, J=8.48, 2 H), 7.40-7.32 (m, 2 H), 7.17 (d, J=8.48 Hz, 2 H), 7.08 (t, J=8.48, 2 H) 2.46 (s, 3 H); MS (EI) m/z 369 (M+H). HRMS Δ=-3.17 mmu.

後処理

  1. temperaturethe mixture refluxed for 60 hours
  2. customto form a fine suspension
  3. temperatureThis suspension was heated
  4. temperatureto reflux for 1.5 hours
  5. temperaturecooled to 50° C.
  6. temperaturereflux
  7. temperatureThis reaction was cooled to room temperature
  8. waitlet stand overnight
  9. washwashed with NaHCO3 saturated solution
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customyielding a brown semi-solid
  14. customchromatographed (9:1 hexane:methylene chloride)

出典と根拠

ORDレコード
ord-364d8840647a46f99c6cb2defab9ba5c
出典データセット
uspto-grants-1997_09
特許番号
US05668161

反応ノート

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