Hydrochloric Acid → Palonosetron

HRID 1590128ノート

反応式

HRID 1590128 の反応式
[CH2:1]([Li])CCC.CCCCCC.[N:12]12[CH2:19][CH2:18][CH:15]([CH2:16][CH2:17]1)[C@H:14]([NH:20][C:21]([C:23]1[C:32]3[CH2:31][CH2:30][CH2:29][CH2:28][C:27]=3[CH:26]=[CH:25][CH:24]=1)=[O:22])[CH2:13]2.CN(C)C=O.Cl>O1CCCC1>[N:12]12[CH2:17][CH2:16][CH:15]([CH2:18][CH2:19]1)[C@H:14]([N:20]1[CH:1]=[C:31]3[CH2:30][CH2:29][CH2:28][C:27]4[C:32]3=[C:23]([CH:24]=[CH:25][CH:26]=4)[C:21]1=[O:22])[CH2:13]2

参加物

7

反応物 5

HCID 313Hydrochloric AcidHCID 6228DimethylformamideHCID 8058HexaneHCID 15656845(S)-N-(1-Azabicyclo[2.2.2]oct-3-yl)-5,6,7,8-tetrahydro-1-naphthalenecarboxamideHCID 178418339Butyllithium

生成物 1

HCID 148210Palonosetron収率 95%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-10 °C

実験手順

A solution of n-butyllithium in hexane (60 mmol) was added dropwise at -70° C. to a solution of (S)-N-(1-azabicyclo[2.2.2]oct-3-yl)-5,6,7,8-tetrahydro1-naphthalenecarboxamide (7.70 g, 21 mmol), prepared as in Example 3, in dry tetrahydrofuran (400 mL). The reaction mixture was stirred at -10° C. for one hour, cooled to -70° C., and dimethylformamide (100 mmol) added in one portion. The reaction mixture was allowed to warm to room temperature over 1.5 hours, then cooled to 0° C. and acidified with 10% aqueous hydrochloric acid. The layers were separated, and the aqueous layer was washed with ethyl acetate, then made basic with 10N aqueous sodium hydroxide and extracted with ethyl acetate. The ethyl acetate was dried over anhydrous sodium sulfate, filtered, and evaporated to give 7.58 g (95% yield) of (S)-2-(1-azabicyclo[2.2.2]oct-3-yl)-2,4,5,6-tetrahydro1H-benz[de]isoquinolin-1-one as white crystals; m.p. 117°-118° C.; [α]D25 +43.2° (c=0.98, CHCl3).

後処理

  1. temperaturecooled to -70° C.
  2. temperatureto warm to room temperature over 1.5 hours
  3. temperaturecooled to 0° C.
  4. customThe layers were separated
  5. washthe aqueous layer was washed with ethyl acetate
  6. extractionextracted with ethyl acetate
  7. dry with materialThe ethyl acetate was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated

出典と根拠

ORDレコード
ord-b08891380cde4ea6bdb903972163b29a
出典データセット
uspto-grants-1993_04
特許番号
US05202333

反応ノート

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