Chloroform → HCID 22930209, compound

HRID 967784Notes

Reaction equation

HRID 967784 reaction equation
[OH:1][C:2]1([CH2:21][N:22]([CH3:33])[C:23]2[CH:32]=[CH:31][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:25][CH:24]=2)[CH2:7][CH2:6][N:5]([C:8](=O)[CH2:9][C:10]2[CH:15]=[CH:14][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:12][CH:11]=2)[CH2:4][CH2:3]1.O1CCCC1.C(Cl)(Cl)Cl.Cl.CO>CO>[OH:1][C:2]1([CH2:21][N:22]([CH3:33])[C:23]2[CH:24]=[CH:25][C:26]([C:27]([O:29][CH3:30])=[O:28])=[CH:31][CH:32]=2)[CH2:7][CH2:6][N:5]([CH2:8][CH2:9][C:10]2[CH:11]=[CH:12][C:13]([S:16]([CH3:19])(=[O:18])=[O:17])=[CH:14][CH:15]=2)[CH2:4][CH2:3]1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 8028TetrahydrofuranHCID 21893726Hydrochloride methanolHCID 69732176HCID 69732176, compound

Product 1

HCID 22930209HCID 22930209, compoundYield 57.6%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Borane-methylsulfide complex (10M; 0.86 mL) was added to a mixture of the compound (1.36 g) obtained in Step 1, anhydrous tetrahydrofuran (15 mL) and anhydrous chloroform (85 mL) under cooling with ice-water over five minutes under nitrogen atmosphere, and the mixture was stirred at room temperature for twenty four hours. After methanol (10 mL) was added to the mixture under cooling with ice-water, hydrogen chloride-methanol reagent (2.5 M; 5.0 mL) was added to adjust pH to below 1 and the mixture was heated under reflux for two hours. The solvent was removed under reduced pressure and to the residue was added chloroform (50 mL) and saturated aqueous sodium hydrogencarbonate solution (50 mL). The mixture was adjusted to pH 10 by using aqueous 2N sodium hydroxide solution (5 mL) and then separated, and the aqueous layer was extracted with chloroform. The organic layer was combined and washed with water and brine successively, and dried over anhydrous sodium sulfate. After the solvent was removed under reduced pressure, the residue was purified by silica gel column chromatography (Chromatorex NH™) (eluent; dichlorometane:methanol=20:1). The fractions were concentrated and the residue was washed with ethyl acetate and dried to obtain the titled compound (0.76 g) as crystals.

Workup

  1. additionwas added
  2. temperaturethe mixture was heated
  3. temperatureunder reflux for two hours
  4. customThe solvent was removed under reduced pressure and to the residue
  5. additionwas added chloroform (50 mL) and saturated aqueous sodium hydrogencarbonate solution (50 mL)
  6. customseparated
  7. extractionthe aqueous layer was extracted with chloroform
  8. washwashed with water and brine successively
  9. dry with materialdried over anhydrous sodium sulfate
  10. customAfter the solvent was removed under reduced pressure
  11. customthe residue was purified by silica gel column chromatography (Chromatorex NH™) (eluent; dichlorometane:methanol=20:1)
  12. concentrationThe fractions were concentrated
  13. washthe residue was washed with ethyl acetate
  14. customdried

Sources & evidence

ORD record
ord-8e38695cdb274ebaaa5cfdfdaf05fd1d
Source dataset
uspto-grants-2005_10
Patent number
US06956046B2

Reaction notes

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