Benzyl chloroformate → HCID 21201599, compound

HRID 1979344Notes

Reaction equation

HRID 1979344 reaction equation
COC[N:4]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:7][CH:6]([NH2:22])[C:5]1=[O:23].[OH-].[Na+].Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]>Br.C(O)(=O)C.O.O1CCCC1>[O:23]=[C:5]1[NH:4][C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[N:8]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][C:16]=2[F:21])[CH2:7][CH:6]1[NH:22][C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]

Participants

7

Reactant 3

HCID 10387Benzyl chloroformateHCID 14798Sodium HydroxideHCID 21201707HCID 21201707, compound

Product 1

HCID 21201599HCID 21201599, compoundYield 40.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 21893785Acetic Acid Mixture with Hydrobromic AcidSolvent

Procedure

1-Methoxymethyl-2-oxo-3-amino-5-(2-fluorophenyl)-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine (0.94 g) was dissolved in 25% hydrobromic acid-acetic acid solution (18 ml), the mixture was stirred for one hour. The reaction mixture was concentrated under reduced pressure, diethyl ether was add, the solid so precipitated was collected by filtration to give pale brown crystals. This crystals were suspended in water (5 ml), 1N aqueous sodium hydroxide (4.5 ml) and a solution of benzyl chloroformate (301 mg) in tetrahydrofuran (7 ml) were added thereto, the resultant mixture was stirred for one hour. Water was added to the reaction mixture, extracted with methylene chloride, the organic layer was successively washed with water and saturated brine, dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1), to thereby obtain 291 mg of the titled compound as amorphous.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure, diethyl ether
  2. additionwas add
  3. customthe solid so precipitated
  4. filtrationwas collected by filtration
  5. customto give pale brown crystals
  6. extractionextracted with methylene chloride
  7. washthe organic layer was successively washed with water and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (n-hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-05fa10be3298461e9a406458f8c6ac33
Source dataset
uspto-grants-2001_05
Patent number
US06239131B1

Reaction notes

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