Bromide ion → (S)-2-(4-bromobenzyl)amino-3-methylbutyric acid

HRID 12593

Reaction equation

HRID 12593 reaction equation
[NH2:1][C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4].C(N([CH:15]([CH3:17])[CH3:16])CC)(C)C.[Br-:18].[OH-].[Na+]>CN(C=O)C.O.C1(C)C=CC=CC=1>[Br:18][C:16]1[CH:15]=[CH:17][C:3]([CH2:4][NH:1][C@H:2]([C:6]([OH:8])=[O:7])[CH:3]([CH3:5])[CH3:4])=[CH:2][CH:6]=1

Participants

8

Reactant 4

HCID 259Bromide ionHCID 6287L-ValineHCID 14798Sodium HydroxideHCID 81531Diisopropylethylamine

Product 1

HCID 11673643(S)-2-(4-bromobenzyl)amino-3-methylbutyric acidYield 153.4%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
22.5 °C

Procedure

52 mL (0.21 mol) of N,O-bistrimethylsilylacetamide is added under nitrogen atmosphere to a mixture made up of 23.5 g (0.20 mol) of L-valine and 38.5 mL (0.22 mol) of diisopropylethylamine in 12.5 mL of DMF. After 1 h at 80° C. the suspension changes to a clear solution. Then, in portions and controlling exothermy, 50 g (0.20 mol) of 4-bromobenzylo bromide is added and left to react at 80° C. for 2 h. The mixture is cooled to 20-25° C., 250 mL of toluene and a solution made up of 250 mL of water and 80 mL of NaOH 40% are added. The resulting aqueous phase is washed twice with 100 mL of AcOEt, the remains of solvent distilled and taken to pH 6-7 with HCl 3N. The solid obtained is filtered with 250 mL of IPA to give 43.9 g (76.5%) of N-(4-bromobenzyl)-L-valine.

Workup

  1. additionis added
  2. waitleft
  3. customto react at 80° C. for 2 h
  4. additionare added
  5. washThe resulting aqueous phase is washed twice with 100 mL of AcOEt
  6. distillationthe remains of solvent distilled
  7. customThe solid obtained
  8. filtrationis filtered with 250 mL of IPA

Sources & evidence

ORD record
ord-145a239c04c24a43b4d3485f843fcd6d
Source dataset
uspto-grants-2010_06
Patent number
US07728021B2

Linked notes

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