Sodium hydride → HCID 19434808, compound

HRID 1736131Notes

Reaction equation

HRID 1736131 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([F:30])[C:5]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]([CH3:19])[CH3:18])=[C:13]([F:20])[CH:12]=3)=[CH:8][C:7](=[O:21])[C:6]=2[C:22]=1[NH:23]C(=O)C(C)(C)C.[H-].[Na+].O1CCCCC1OC1CCCCO1.I[CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][OH:53].[Cl-].[NH4+]>CN(C)C=O>[F:1][C:2]1[CH:3]=[C:4]([F:30])[C:5]2[O:10][C:9]([C:11]3[CH:16]=[CH:15][C:14]([N:17]([CH3:18])[CH3:19])=[C:13]([F:20])[CH:12]=3)=[CH:8][C:7](=[O:21])[C:6]=2[C:22]=1[NH:23][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][OH:53]

Participants

7

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium ChlorideHCID 263182Tetrahydropyranyl etherHCID 130890816-Iodo-1-hexanolHCID 19434956HCID 19434956, compound

Product 1

HCID 19434808HCID 19434808, compoundYield 70%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

1.0 g (2.99 mmol) of Compound 38 obtained in Example 38 was dissolved in 20 ml of dimethylformamide under argon atmosphere, 239 mg of sodium hydride (60% oil dispersion) and 1.87 g of tetrahydropyranyl ether of 6-iodo-1-hexanol were added under ice-cooling and the mixture was stirred at 0° C. for 1.3 hours. An aqueous saturated solution of ammonium chloride was added to the reaction solution and the mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. 18 ml of ethanol and 2 ml of concentrated hydrochloric acid were added to the residue and the mixture was stirred at room temperature for 18 hours. The reaction solution was adjusted to pH 7 by addition of a 10N aqueous solution of sodium hydroxide thereto, and the mixture was extracted with ethyl acetate. The organic layer was washed with an aqueous saturated solution of sodium chloride and dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (chloroform: methanol=40:1) and recrystallized from n-hexane/ethyl acetate to give 912 mg (70%) of Compound 60.

Workup

  1. temperaturecooling
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled off under reduced pressure
  6. addition18 ml of ethanol and 2 ml of concentrated hydrochloric acid were added to the residue
  7. stirringthe mixture was stirred at room temperature for 18 hours
  8. additionThe reaction solution was adjusted to pH 7 by addition of a 10N aqueous solution of sodium hydroxide
  9. extractionthe mixture was extracted with ethyl acetate
  10. washThe organic layer was washed with an aqueous saturated solution of sodium chloride
  11. dry with materialdried over anhydrous sodium sulfate
  12. distillationthe solvent was distilled off under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (chloroform: methanol=40:1)
  14. customrecrystallized from n-hexane/ethyl acetate

Sources & evidence

ORD record
ord-7728e9370c704d789c187c494eef4db4
Source dataset
uspto-grants-1996_07
Patent number
US05539112

Reaction notes

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