Tetrahydrofuran → HCID 21251983, compound

HRID 1532453Notes

Reaction equation

HRID 1532453 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].O1[CH2:11][CH2:10][CH2:9][CH2:8]1.[Cl:12][C:13]1[CH:14]=[C:15]2[N:24]=[CH:23][N:22]3[C:16]2=[C:17]([CH:31]=1)[CH2:18][N:19]([CH2:26][CH:27]=[C:28](C)C)[C@@H:20](C)[CH2:21]3.[OH-:32].[Na+]>O>[ClH:12].[C:17]1([CH2:18][N:19]2[CH2:26][C:27]3[CH:28]=[CH:11][CH:10]=[C:9]4[NH:24][C:23](=[O:32])[N:22]([C:8]=34)[CH2:21][CH2:20]2)[CH:16]=[CH:15][CH:14]=[CH:13][CH:31]=1

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 21226445Aluminium lithium hydrideHCID 86756542HCID 86756542, compound

Product 1

HCID 21251983HCID 21251983, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
200 °C

Procedure

To a mixture of 6.84 parts of lithium aluminum hydride and 90 parts of tetrahydrofuran there was added a solution of 9 parts of intermediate 2 in 90 parts of tetrahydrofuran. After stirring for 2½ hour, there were added successively water and NaOH 15% while cooling on ice. The whole was filtered and the filtrate was evaporated. The residue was taken up in methylbenzene and this solution was dried, filtered and evaporated. The residue was heated at 200° C. for 10 min with 2 parts of urea. At 100° C., the whole was diluted with 25 parts of boiling water. The aqueous layer was decanted and the residue was treated with activated charcoal in a mixture of 35 parts of HCl (1N) and 35 parts of water. After filtration, the mixture was basified with NH4OH and the product was extracted with methylbenzene (80 parts and 40 parts). The combined extracts were dried, filtered and evaporated. The residue was crystallized from 4-methyl-2-pentanone and then converted into the monohydrochloride salt in methanol by addition of 2-propanol saturated with HCl. The salt was filtered off, recrystallized from water and dried, yielding 3.2 parts of 6-(phenylmethyl)-4,5,6,7-tetrahydroimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one monohydrochloride; mp. 258.5-262° C. (comp. 1).

Workup

  1. temperaturewhile cooling on ice
  2. filtrationThe whole was filtered
  3. customthe filtrate was evaporated
  4. customthis solution was dried
  5. filtrationfiltered
  6. customevaporated
  7. additionAt 100° C., the whole was diluted with 25 parts of boiling water
  8. customThe aqueous layer was decanted
  9. additionthe residue was treated with activated charcoal in a mixture of 35 parts of HCl (1N) and 35 parts of water
  10. filtrationAfter filtration
  11. extractionthe product was extracted with methylbenzene (80 parts and 40 parts)
  12. customThe combined extracts were dried
  13. filtrationfiltered
  14. customevaporated
  15. customThe residue was crystallized from 4-methyl-2-pentanone
  16. additionconverted into the monohydrochloride salt in methanol by addition of 2-propanol saturated with HCl
  17. filtrationThe salt was filtered off
  18. customrecrystallized from water
  19. customdried

Sources & evidence

ORD record
ord-384ea20c92f94243af1b3b593a8780dc
Source dataset
uspto-grants-2001_03
Patent number
US06201119B1

Reaction notes

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