Ammonium Chloride → HCID 131715773, compound

HRID 2231820Notes

Reaction equation

HRID 2231820 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][CH2:6]Br.[Mg].[Cl:9][C:10]1[CH:18]=[CH:17][C:16]2[N:15]3[CH2:19][CH2:20][CH2:21][N:22]=[C:14]3[C:13](=[O:23])[C:12]=2[CH:11]=1.[NH4+].[Cl-]>CCOCC.ClCCl>[ClH:9].[Cl:9][C:10]1[CH:18]=[CH:17][C:16]2[N:15]3[CH2:19][CH2:20][CH2:21][N:22]=[C:14]3[C:13]([OH:23])([CH2:6][CH2:5][CH2:4][CH2:3][O:2][CH3:1])[C:12]=2[CH:11]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 5211681-Bromo-4-methoxybutaneHCID 5462224MagnesiumHCID 21284813HCID 21284813, compound

Product 1

HCID 131715773HCID 131715773, compoundYield 132.5%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

A Grignard reagent was prepared from 4-methoxybutyl bromide (5 g) and magnesium (0.72 g) in dry ether (25 ml). After cooling with an ice-bath, under a blanket of nitrogen, a solution of 8-chloro-3,4-dihydropyrimido[1,2-a]indol-10(2H)-one (2.2 g) in dichloromethane (25 ml) was added slowly. When addition was complete the mixture was stirred at room temperature for 3 hours. It was poured onto saturated aqueous NH4Cl, the layers were separated and the aqueous phase extracted with dichloromethane. The combined organic phases were washed with water and dried (MgSO4). Filtration and evaporation gave an orange solid, which was triturated with boiling ethyl acetate, cooled, filtered and the crystals were washed with hexane. The crystals were suspended in boiling ethanol and acidified with ethanolic HCl. Evaporation of the solution gave a solid which crystallised from isopropanol. Two crops were combined and dried at 50°/1 mm to give pure 8-chloro-10-hydroxy-10-(4-methoxybutyl)-2,3,4,10-tetrahydropyrimido[1,2-a]indole, hydrochloride quarter hydrate (2.28 g) as buff-cream crystals, m.p. 218°-221° (dec).

Workup

  1. temperatureAfter cooling with an ice-bath, under a blanket of nitrogen
  2. additionWhen addition
  3. customthe layers were separated
  4. extractionthe aqueous phase extracted with dichloromethane
  5. washThe combined organic phases were washed with water
  6. dry with materialdried (MgSO4)
  7. filtrationFiltration and evaporation
  8. customgave an orange solid, which
  9. customwas triturated with boiling ethyl acetate
  10. temperaturecooled
  11. filtrationfiltered
  12. washthe crystals were washed with hexane
  13. customEvaporation of the solution
  14. customgave a solid which
  15. customcrystallised from isopropanol
  16. customdried at 50°/1 mm

Sources & evidence

ORD record
ord-16dd1e31b39847d783f8ebc98d33e632
Source dataset
uspto-grants-1988_11
Patent number
US04784996

Reaction notes

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