Sodium hydride → 3-[4-methyl-3-(2-propynyloxy)phenyl]-6-(trifluoromethyl)-2,4-(1H,3H)-pyrimidinedione

HRID 654737

反応式

HRID 654737 の反応式
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][C:3]=1[O:9][CH2:10][C:11]#[CH:12].[N-:13]=[C:14]=[O:15].N(C1(C)C=CC=C(OCC#C)C1)=C=O.N[C:31]([C:38]([F:41])([F:40])[F:39])=[CH:32][C:33](OCC)=[O:34].[Na].[H-].[Na+]>C(Cl)(Cl)=O.C(OCC)(=O)C.C1COCC1>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:33](=[O:34])[CH:32]=[C:31]([C:38]([F:41])([F:40])[F:39])[NH:13][C:14]2=[O:15])=[CH:4][C:3]=1[O:9][CH2:10][C:11]#[CH:12]

参加物

10

反応物 6

HCID 24758Sodium hydrideHCID 105034Isocyanate2 回HCID 136209Ethyl 3-amino-4,4,4-trifluoro-2-butenoateHCID 5360545SodiumHCID 146773494-Methyl-3-(prop-2-yn-1-yloxy)anilineHCID 867460114-Isocyanato-4-methyl-2-(2-propynyloxy)benzene

生成物 1

HCID 540595403-[4-methyl-3-(2-propynyloxy)phenyl]-6-(trifluoromethyl)-2,4-(1H,3H)-pyrimidinedione

試薬・触媒・溶媒 3

HCID 6371Phosgene溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
-62 °C

実験手順

As described above 1-methyl-4-nitro-2-(2-propynyloxy)benzene was made, mp 75°-77° C. This compound, (26 g) was reduced using iron in ethanol and water to give 4-methyl-3-(2-propynyloxy)benzenamine isolated as the hydrochloride salt mp >250° C. This amine salt was converted to the isocyanate analogue using phosgene in ethyl acetate as solvent, i.e. 4-isocyanato-4-methyl- 2-(2-propynyloxy)benzene, bp 78°-80° C./0.05 mm. Ethyl 3-amino-4,4,4-trifluoro-2-butenoate (19.6 g) was converted to its sodium salt using sodium hydride (4.6 g., 60%) in THF (100 ml). This solution was chilled to -62° C. and treated with a solution of the isocyanate (20 g) in THF (15 ml) over 2 minutes. The reaction warmed to -48° C. before cooling again. After stirring to ambient temperature and overnight the solvent was removed, water (250 ml) added, filtered to remove the precipitate and acidified whereupon a second precipitate was obtained. This solid was collected on a filter washed with water and re-extracted into aqueous sodium bicarbonate. After filtering the clear filtrate was acidified and the resulting cream precipitate was collected on a filter, washed with water and dried to give 3-[4-methyl-3-(2-propynyloxy)phenyl]-6- (trifluoromethyl)-2,4-(1H,3H)-pyrimidinedione, mp 202°-204° C.

後処理

  1. temperatureThe reaction warmed to -48° C.
  2. temperaturebefore cooling again
  3. customwas removed
  4. additionwater (250 ml) added
  5. filtrationfiltered
  6. customto remove the precipitate
  7. customwas obtained
  8. customThis solid was collected on a filter
  9. washwashed with water
  10. extractionre-extracted into aqueous sodium bicarbonate
  11. filtrationAfter filtering the clear filtrate
  12. customthe resulting cream precipitate was collected on a filter
  13. washwashed with water
  14. customdried

出典と根拠

ORDレコード
ord-9f68509890a64cf8a780ed70ac44f285
出典データセット
uspto-grants-1992_07
特許番号
US05134144

関連ノート

読み込み中…