Sodium Hydroxide → HCID 67792189, compound

HRID 467002Notes

Reaction equation

HRID 467002 reaction equation
[F:1][C:2]1[CH:31]=[CH:30][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][CH:27]([OH:28])[C:20]5=[N:19][C:18]=4[CH3:29])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1.[C:32]([Cl:43])(=[O:42])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41].[OH-].[Na+]>O.ClCCl>[ClH:43].[ClH:43].[F:1][C:2]1[CH:31]=[CH:30][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][CH:27]([O:28][C:32](=[O:42])[CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH3:41])[C:20]5=[N:19][C:18]=4[CH3:29])[CH2:11][CH2:10]3)=[N:7][O:8][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 66982Decanoyl chloride2×HCID 115237Paliperidone

Product 1

HCID 67792189HCID 67792189, compoundYield 45.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of 1.2 parts of 3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyrido[1,2-a]-pyrimidin-4-one in 21 parts of dichloromethane and 5 parts of water were simultaneously added dropwise a solution of 1.1 parts of decanoyl chloride in 13 parts of dichloromethane and a solution of 1 part of sodium hydroxide in 6 parts of water. Upon complete addition, stirring was continued for 2 hours at room temperature. Another portion of 1.1 parts of decanoyl chloride was added and stirring was continued overnight at room temperature. The product was extracted with dichloromethane. The extract was washed with water, 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 pure fractions were collected and the eluent was evaporated. The residue was converted into the hydrochloride salt in 2-propanol. The product was filtered off and dried, yielding 0.9 parts (45.9%) of [3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]ethyl]-6,7,8,9-tetrahydro-2-methyl-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl]decanoate dihydrochloride; mp. 221.4° C. (Compound 6)

Workup

  1. additionUpon complete addition
  2. stirringstirring
  3. waitwas continued overnight at room temperature
  4. extractionThe product was extracted with dichloromethane
  5. washThe extract was washed with water
  6. customdried
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by column chromatography over silica gel using
  10. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
  11. customThe pure fractions were collected
  12. customthe eluent was evaporated
  13. filtrationThe product was filtered off
  14. customdried

Sources & evidence

ORD record
ord-6940df0888c34df6a2aecfa8caf076d9
Source dataset
uspto-grants-1992_10
Patent number
US05158952

Reaction notes

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