Sodium Hydroxide → HCID 13851195, compound

HRID 978454Notes

Reaction equation

HRID 978454 reaction equation
Cl.[F:2][C:3]1[CH:31]=[CH:30][C:6]([C:7]([CH:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][N:17]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([OH:28])[CH:24]=4)[NH:19][C:18]3=[S:29])[CH2:11][CH2:10]2)=[O:8])=[CH:5][CH:4]=1.[OH-].[Na+].[BH4-].[Na+].[OH-].[NH4+]>ClC(Cl)Cl.C(O)=O.O.CO>[F:2][C:3]1[CH:31]=[CH:30][C:6]([CH:7]([OH:8])[CH:9]2[CH2:10][CH2:11][N:12]([CH2:15][CH2:16][N:17]3[C:26](=[O:27])[C:25]4[C:20](=[CH:21][CH:22]=[C:23]([OH:28])[CH:24]=4)[NH:19][C:18]3=[S:29])[CH2:13][CH2:14]2)=[CH:5][CH:4]=1

Participants

9

Reactant 4

HCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 4311764Sodium borohydrideHCID 20202895HCID 20202895, compound

Product 1

HCID 13851195HCID 13851195, compoundYield 28.5%

Reagents, catalysts & solvents 4

HCID 284Formic AcidSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 6212ChloroformSolvent

Procedure

To a stirred solution of 2.3 parts of 3-[2-[4-(4-fluorobenzoyl)-1-piperidinyl]ethyl]-2,3-dihydro-6-hydroxy-2-thioxo-4(1H)-quinazolinone monohydrochloride in 40 parts of methanol was added a sodium hydroxide solution 1N till pH=7. 0.37 Parts of sodium borohydride were added portionwise. Upon completion, stirring was continued for 20 hours at room temperature. The reaction mixture was poured into water. The whole was acidified with formic acid till pH=2. After stirring for 30 minutes at room temperature, the mixture was treated with ammonium hydroxide (an oily precipitate was formed). Trichloromethane was added. After 1 hour, the only precipitate was dissolved. The organic layer was separated and washed with water whereupon a precipitate was formed (=precipitate I). Then the organic layer was washed again with water, dried, filtered and evaporated (=residue I). Precipitate I and residue I were purified by column chromatography over silica gel using first a mixture of trichloromethane and methanol (90:10 by volume) and then a mixture of trichloromethane and methanol (80:20 by volume) as eluent. The second fraction was collected and the eluent was evaporated. The residue was boiled in 20 parts of 2-propanone and 17.5 parts of 2,2'-oxybispropane. The product was filtered off and dried at 100° C., yielding 0.6 parts (28.5%) of 3-[2-[4-[(4-fluorophenyl)hydroxymethyl]-1-piperidinyl]ethyl]-2,3-dihydro-6-hydroxy-2-thioxo-4(1H)-quinazolinone; mp. 218.0° C. (25). Following the same procedure and using equivalent amount of the appropriate starting materials there was also prepared:

Workup

  1. stirringAfter stirring for 30 minutes at room temperature
  2. customwas formed)
  3. waitAfter 1 hour
  4. dissolutionthe only precipitate was dissolved
  5. customThe organic layer was separated
  6. washwashed with water whereupon a precipitate
  7. customwas formed (=precipitate I)
  8. washThen the organic layer was washed again with water
  9. customdried
  10. filtrationfiltered
  11. customevaporated (=residue I)
  12. customPrecipitate I and residue I were purified by column chromatography over silica gel using first
  13. additiona mixture of trichloromethane and methanol (90:10 by volume)
  14. additiona mixture of trichloromethane and methanol (80:20 by volume) as eluent
  15. customThe second fraction was collected
  16. customthe eluent was evaporated
  17. filtrationThe product was filtered off
  18. customdried at 100° C.

Sources & evidence

ORD record
ord-5cfbb022cd4c444ab948f86f39bafffb
Source dataset
uspto-grants-1987_05
Patent number
US04665075

Reaction notes

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