Acetic Acid → HCID 178476272, compound

HRID 80578Notes

Reaction equation

HRID 80578 reaction equation
[NH2:1][C:2]1[CH:10]=[C:9]([C@H:11]([NH:15][C:16]([N:18]2[C:24](=[O:25])[C@@H:23]([CH2:26][C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=3[O:34][CH3:35])[CH2:22][NH:21][C:20](=[N:36][O:37][CH2:38][CH3:39])[CH2:19]2)=[O:17])[CH2:12][CH2:13][CH3:14])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].C(O)(=O)C.O.C(O)(=O)C.O>C(OCC)(=O)C>[C:4]([OH:6])(=[O:5])[CH3:3].[NH2:1][C:2]1[CH:10]=[C:9]([C@H:11]([NH:15][C:16]([N:18]2[C:24](=[O:25])[C@@H:23]([CH2:26][C:27]3[CH:32]=[C:31]([Cl:33])[CH:30]=[CH:29][C:28]=3[O:34][CH3:35])[CH2:22][NH:21]/[C:20](=[N:36]\[O:37][CH2:38][CH3:39])/[CH2:19]2)=[O:17])[CH2:12][CH2:13][CH3:14])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 21899381Acetic acid--water (1/1)HCID 178448362HCID 178448362, compound

Product 1

HCID 178476272HCID 178476272, compoundYield 175.8%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

The reaction mixture was diluted with ethyl acetate (10 ml) and filtered by a glass filter spread with Celite®, and further the residue was washed with ethyl acetate (20 ml). The filtrate and the washings were combined, then successively washed with saturated aqueous ammonium chloride solution and brine, dried over sodium sulfate, then concentrated. The concentrated residue was purified by flash column chromatography to obtain 2-amino-4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3-(ethoxyimino)-7-oxo-1,4-diazepan-1-yl]carbonyl}amino)butyl]benzoic acid (compound 12) (698 mg). To the compound 12 (558 mg) thus obtained, acetic acid (1.1 ml) was added and the mixture was stirred at room temperature for 30 minutes. Then water (2.75 ml) was added, and the mixture was stirred for 10 minutes. Further, acetic acid/water (2/5, 2.5 ml) was added, and the mixture was stirred for 15 minutes, then the mixture was cooled to 0° C. and stirred for 30 minutes. The precipitated crystals were collected by filtration to obtain the title compound (543 mg) as a light yellow crystals.

Workup

  1. filtrationfiltered by a glass
  2. filtrationfilter
  3. washfurther the residue was washed with ethyl acetate (20 ml)
  4. washsuccessively washed with saturated aqueous ammonium chloride solution and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe concentrated residue was purified by flash column chromatography
  8. customto obtain 2-amino-4-[(1R)-1-({[(6S)-6-(5-chloro-2-methoxybenzyl)-3-(ethoxyimino)-7-oxo-1,4-diazepan-1-yl]carbonyl}amino)butyl]benzoic acid (compound 12) (698 mg)
  9. stirringthe mixture was stirred for 10 minutes
  10. stirringthe mixture was stirred for 15 minutes
  11. temperaturethe mixture was cooled to 0° C.
  12. stirringstirred for 30 minutes
  13. filtrationThe precipitated crystals were collected by filtration

Sources & evidence

ORD record
ord-5f782b3f875644eb9be878436f503120
Source dataset
uspto-grants-2014_09
Patent number
US08846660B2

Reaction notes

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