Ethanol → Risperidal iMpurity B

HRID 969736노트

반응식

HRID 969736 반응식
[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[C:4]([CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][C:14]2[C:19](=[O:20])[N:18]3[CH2:21][CH2:22][CH2:23][CH2:24][C:17]3=[N:16][C:15]=2[CH3:25])[CH2:8][CH2:7]1)=O.Cl.[NH2:32][OH:33].C(O)C.[OH-].[K+]>N1C=CC=CC=1>[F:1][C:2]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:3]=1[C:4](=[N:32][OH:33])[CH:6]1[CH2:11][CH2:10][N:9]([CH2:12][CH2:13][C:14]2[C:19](=[O:20])[N:18]3[CH2:21][CH2:22][CH2:23][CH2:24][C:17]3=[N:16][C:15]=2[CH3:25])[CH2:8][CH2:7]1

참가 물질

6

반응물 4

HCID 702EthanolHCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 29941101DES(6-fluoro-1,2-benzoxazole)-2,4-difluorobenzoyl risperidone

생성물 1

HCID 71433889Risperidal iMpurity B수율 68.2%

시약·촉매·용매 1

HCID 1049Pyridine용매

실험 절차

To a solution of 7.0 g (0.0143 mole) of 3-[2-[4-(2,4-difluoro-benzoyl)-piperidino]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one, 70 ml of pyridine, 5.4 g (0.0777 mole) of hydroxylamine hydrochloride and 100 ml of ethanol 1.6 g (0.0286 mole) of potassium hydroxide are added. The reaction mixture is heated to boiling for 10 hours, cooled to room temperature and the solvent is removed in vacuo. To the residue 100 ml of water are added and the mixture is extracted with 100 ml of dichloromethane. The organic phase is washed twice with 50 ml of water each, dried over anhydrous magnesium sulfate and evaporated. The residual crude product is recrystallized from ethyl acetate. Thus 4.2 g of 3-[2-[4-[(2,4-difluorophenyl)-(hydroxyimino)-methyl]-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4H-pyrido[1,2-a]pyrimidin-4-one are obtained. Yield 65.1%. According to HPLC analysis the purity of the product is 97.2%.

후처리

  1. temperatureThe reaction mixture is heated
  2. customthe solvent is removed in vacuo
  3. additionTo the residue 100 ml of water are added
  4. extractionthe mixture is extracted with 100 ml of dichloromethane
  5. washThe organic phase is washed twice with 50 ml of water each,
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated
  8. customThe residual crude product is recrystallized from ethyl acetate

출처 및 근거

ORD 기록
ord-15f65e5267c9440d975507418ae315fc
출처 데이터셋
uspto-grants-2007_12
특허 번호
US07307168B2

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