Trimethylsilyl iodide → 9-OH-risperidone

HRID 467003ノート

反応式

HRID 467003 の反応式
[F:1][C:2]1[CH:32]=[CH:31][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][C:17]4[C:22](=[O:23])[N:21]5[CH2:24][CH:25]([O:28]C)[CH2:26][CH2:27][C:20]5=[N:19][C:18]=4[CH3:30])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.I[Si](C)(C)C>C(#N)C>[F:1][C:2]1[CH:32]=[CH:31][C:5]2[C:6]([CH:9]3[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][C:17]4[C:22](=[O:23])[N:21]5[CH2:24][CH:25]([OH:28])[CH2:26][CH2:27][C:20]5=[N:19][C:18]=4[CH3:30])[CH2:13][CH2:14]3)=[N:7][O:8][C:4]=2[CH:3]=1

参加物

4

反応物 2

HCID 85247Trimethylsilyl iodide2 回HCID 183536403-(2-(4-(6-Fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl)ethyl)-6,7,8,9-tetrahydro-7-methoxy-2-methyl-4H-pyrido(1,2-a)pyrimidin-4-one

生成物 1

HCID 4751009-OH-risperidone収率 3.7%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

反応条件

温度
70 °C

実験手順

A mixture of 8.5 parts of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]-6,7,8,9-tetrahydro-7-methoxy-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one, 14 parts of iodotrimethylsilane and 40 parts of acetonitrile was stirred overnight at 70° C. Another portion of 2.8 parts of iodotrimethylsilane was added and the reaction mixture was stirred for a while at 90° C. and then overnight at reflux temperature. After cooling, the whole was evaporated. The residue was taken up in ethanol and the whole was evaporated again. The residue was taken up in water and treated with a sodium hydroxide solution. The product was extracted with trichloromethane. The extract was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The desired fraction was collected and the eluent was evaporated. The residue was solidified in ethanol. The product was filtered off and dried, yielding 0.3 parts (3.7%) of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-7-hydroxy-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one; mp. 156.2° C. (Compound 7)

後処理

  1. stirringthe reaction mixture was stirred for a while at 90° C.
  2. temperatureovernight at reflux temperature
  3. temperatureAfter cooling
  4. customthe whole was evaporated
  5. customthe whole was evaporated again
  6. additiontreated with a sodium hydroxide solution
  7. extractionThe product was extracted with trichloromethane
  8. customThe extract was dried
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by column chromatography over silica gel using
  12. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  13. customThe desired fraction was collected
  14. customthe eluent was evaporated
  15. filtrationThe product was filtered off
  16. customdried

出典と根拠

ORDレコード
ord-d136789a677d4b56b3b2e8b6c2ef2cca
出典データセット
uspto-grants-1992_10
特許番号
US05158952

反応ノート

読み込み中…