Sodium cyanoborohydride → Risperidone

HRID 1271537Notes

Reaction equation

HRID 1271537 reaction equation
[F:1][C:2]1[CH:30]=[CH:29][C:5]2[C:6]([CH:9]3[CH2:14][CH2:13][N:12]([CH:15]=[CH:16][C:17]4[C:22](=[O:23])[N:21]5[CH2:24][CH2:25][CH2:26][CH2:27][C:20]5=[N:19][C:18]=4[CH3:28])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.C([BH3-])#N.[Na+]>C(O)C.C(O)(=O)C.C(OCC)(=O)C>[F:1][C:2]1[CH:30]=[CH:29][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][CH2:25][CH2:26][CH2:27][C:20]5=[N:19][C:18]=4[CH3:28])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 2

HCID 5003444Sodium cyanoborohydrideHCID 865989853-{2-[4-(6-Fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl]-vinyl}-2-methyl-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidin-4-one

Product 1

HCID 5073RisperidoneYield 83.3%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a suspension of 1.39 g (3,42 mmoles) of 3-{2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl]-vinyl}-2-methyl-6,7,8,9-tetrahydro-pyrido[1,2-a]pyrimidin-4-one (III) in 22 mL of absolute ethanol and 1 mL of glacial acetic acid under stirring at room temperature and in a protective atmosphere, 0.254 g (4.04 mmoles) of sodium cyanoborohydride in small portions was added for 1 hour. After 1.5 hour, the solvent was evaporated and the crude product obtained was dissolved in 250 mL of ethyl acetate. The organic phase was successively washed with 50 mL of 1M aqueous sodium bicarbonate solution, 50 mL of water and 50 mL of saturated sodium chloride solution and dried over anhydrous magnesium sulphate. The resultant solution was filtered and the solvent was evaporated to yield 1.17 g of a residual solid (83%), which was diluted in methylene chloride and purified by column chromatography (silica gel). Elution of the column was with methylene chloride, methanol and triethylamine (95:5:1). The pure fractions were collected and the solvent was evaporated under reduced pressure to give 0.83 g (70.9%) of 3-{2-[4-(6-fluorobenzo[d]isoxazol-3-yl)-piperidin-1-yl]-ethyl}-2-methyl-6,7,8,9-tetrahydro-4H-pyrido-[1,2-a]pyrimidin-4-one (I). Optionally, the reaction crude product was purified by crystallization from a suitable organic solvent, preferably ethanol or 4-methyl-2-pentanone.

Workup

  1. additionwas added for 1 hour
  2. customthe solvent was evaporated
  3. customthe crude product obtained
  4. washThe organic phase was successively washed with 50 mL of 1M aqueous sodium bicarbonate solution, 50 mL of water and 50 mL of saturated sodium chloride solution
  5. dry with materialdried over anhydrous magnesium sulphate
  6. filtrationThe resultant solution was filtered
  7. customthe solvent was evaporated

Sources & evidence

ORD record
ord-b4c9375979794d90b18fc4a6791813e2
Source dataset
uspto-grants-2007_04
Patent number
US07205405B2

Reaction notes

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