Sodium hydride → HCID 19360231, compound

HRID 376886Notes

Reaction equation

HRID 376886 reaction equation
[H-].[Na+].[Cl:3][C:4]1[C:9]2[S:10][CH:11]=[C:12]([NH:13][C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[C:8]=2[CH:7]=[CH:6][CH:5]=1.C1O[C:23]([C:28]2[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=2)([CH2:24][CH2:25][CH2:26]Cl)[O:22]C1>CN(C=O)C.CO>[ClH:3].[Cl:3][C:4]1[C:9]2[S:10][CH:11]=[C:12]([N:13]([CH2:26][CH2:25][CH2:24][C:23](=[O:22])[C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)[C:14]3[CH:19]=[CH:18][N:17]=[CH:16][CH:15]=3)[C:8]=2[CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 27237782-(3-Chloropropyl)-2-(4-fluorophenyl)-1,3-dioxolaneHCID 19360126HCID 19360126, compound

Product 1

HCID 19360231HCID 19360231, compoundYield 67.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolvent2×HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

To a mixture of sodium hydride (645 mg, 16.13 mmole) in DMF (10 mL) was added dropwise a solution of 7-chloro-3-(4-pyridinyl)aminobenzo[b]thiophene (3.5 g, 13.44 mmole) in DMF (35 mL) and then 4'-fluoro-4-chlorobutyrophenone ethylene ketal (3.95 g, 16.13 mmole) was added. This mixture was heated with stirring at 70° C. for three hours, poured into ice and extracted with ethyl acetate. The organics were washed twice with water, dried (MgSO4), and then concentrated. The residue was flash chromatographed (silica gel; EtOAc, then 5% MeOH/EtOAc) to obtain a dark oil, which was dissolved in methanol and treated with "Norite" to obtain 2.88 g of a white froth after concentration. Concentrated HCl (30 mL) was added and the mixture was heated on a steam bath for 45 minutes. The reaction mixture was cooled, made basic with 10% sodium hydroxide and extracted with diethyl ether. The organics were washed with water and brine, dried (MgSO4), and concentrated to obtain a froth. The froth was dissolved in methanol and ethereal hydrogen chloride, concentrated, and the frothy oil was triturated with diethyl ether. The organics were decanted and the resulting solid was recrystallized from methanol and diethyl ether to obtain 2.09 g of a white solid, mp 229° C. (dec.), after drying under high vacuum, P2O5, and refluxing xylenes.

Workup

  1. temperatureThis mixture was heated
  2. additionpoured into ice
  3. extractionextracted with ethyl acetate
  4. washThe organics were washed twice with water
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated
  7. customchromatographed (silica gel
  8. customEtOAc, then 5% MeOH/EtOAc) to obtain a dark oil, which
  9. additiontreated with "Norite"
  10. customto obtain 2.88 g of a white froth
  11. concentrationafter concentration
  12. additionConcentrated HCl (30 mL) was added
  13. temperaturethe mixture was heated on a steam bath for 45 minutes
  14. temperatureThe reaction mixture was cooled
  15. extractionextracted with diethyl ether
  16. washThe organics were washed with water and brine
  17. dry with materialdried (MgSO4)
  18. concentrationconcentrated
  19. customto obtain a froth
  20. concentrationethereal hydrogen chloride, concentrated
  21. customthe frothy oil was triturated with diethyl ether
  22. customThe organics were decanted
  23. customthe resulting solid was recrystallized from methanol and diethyl ether

Sources & evidence

ORD record
ord-ad21ed2b396f475d9d0d25d56351de0f
Source dataset
uspto-grants-2000_02
Patent number
US06022880

Reaction notes

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