Benzyl Bromide → HCID 20254477, compound

HRID 2413286Notes

Reaction equation

HRID 2413286 reaction equation
[C:1]([NH:4][C:5]([CH:23]([F:25])[F:24])([CH2:9][CH2:10][CH2:11][NH:12][C:13]([O:15]CC1C=CC=CC=1)=O)[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2].C(Br)C1C=CC=CC=1.[CH:34]1([NH:40]C2CCCCC2)CCCC[CH2:35]1>CN(C)C=O>[C:1]([NH:4][C:5]([CH:23]([F:24])[F:25])([CH2:9][CH2:10][CH2:11][NH:12][C:13](=[O:15])[CH:34]([NH2:40])[CH3:35])[C:6]([OH:8])=[O:7])(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 7582DicyclohexylamineHCID 20254457HCID 20254457, compound

Product 1

HCID 20254477HCID 20254477, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 0.5 g of 2-acetylamino-5-benzyloxycarbonylamino-2-difluoromethylpentanoic acid in 4 ml of dimethylformamide is added 0.27 g of benzylbromide and 0.4 ml of dicyclohexylamine. The reaction mixture is stirred for 12 hours and then the precipitate is filtered off. The filtrate is evaporated under reduced pressure, and the residue is partitioned between ethylacetate and water. The organic phase is washed with aqueous hydrochloric acid, water, 5% sodium bicarbonate, water and brine then dried over magnesium sulfate. The solvent is evaporated and the residue heated in 5 ml of trifluoroacetic acid for 1 hour at room temperature. The excess trifluoroacetic acid is then stripped off under reduced pressure. The residue is suspended in 5 ml of ether and a solution of N-benzyloxycarbonyl-O-ethoxycarbonylalanine (0.4 g) and triethylamine (0.2 g) in 5 ml of ether is added. Stirring is continued overnight at room temperature. The solvent is evaporated. The resulting syrupy residue is dissolved in glacial acetic acid, and the solution hydrogenated over Pd/C 10% (30 mg) for 12 hours. The catalyst is then filtered off. The filtrate is concentrated and the residue purified by ion exchange chromatography on an Amberlite 120 acidic column to give 2-acetylamino-5-(2-aminopropionylamino)-2-difluoromethylpentanoic acid.

Workup

  1. filtrationthe precipitate is filtered off
  2. customThe filtrate is evaporated under reduced pressure
  3. customthe residue is partitioned between ethylacetate and water
  4. washThe organic phase is washed with aqueous hydrochloric acid, water, 5% sodium bicarbonate, water and brine
  5. dry with materialthen dried over magnesium sulfate
  6. customThe solvent is evaporated
  7. additiona solution of N-benzyloxycarbonyl-O-ethoxycarbonylalanine (0.4 g) and triethylamine (0.2 g) in 5 ml of ether is added
  8. stirringStirring
  9. waitis continued overnight at room temperature
  10. customThe solvent is evaporated
  11. dissolutionThe resulting syrupy residue is dissolved in glacial acetic acid
  12. waitthe solution hydrogenated over Pd/C 10% (30 mg) for 12 hours
  13. filtrationThe catalyst is then filtered off
  14. concentrationThe filtrate is concentrated
  15. customthe residue purified by ion exchange chromatography on an Amberlite 120 acidic column

Sources & evidence

ORD record
ord-16cec00cb1074547ace47747cb716116
Source dataset
uspto-grants-1985_01
Patent number
US04496588

Reaction notes

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