Benzyl Bromide → (s)-2-Benzyloxy-4-benzyloxycarbonylaminobutyric acid

HRID 1775758Notes

Reaction equation

HRID 1775758 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C@H:14]([OH:18])[C:15]([OH:17])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-2].[Ba+2].O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].[CH2:32](Br)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN(C)C=O.C(Cl)(Cl)Cl.Cl.O.C(O)(=O)C.C(OCC)(=O)C>[CH2:32]([O:18][C@@H:14]([CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[C:15]([OH:17])=[O:16])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

11

Reactant 4

HCID 7498Benzyl BromideHCID 2733930(S)-2-Hydroxy-4-(((phenylmethoxy)carbonyl)amino)butyric acidHCID 9855530Barium Oxide Nanoparticle Dispersion2×HCID 17749109Barium hydroxide, octahydrate

Product 1

HCID 57784532(s)-2-Benzyloxy-4-benzyloxycarbonylaminobutyric acid

Reagents, catalysts & solvents 6

HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent2×HCID 6212ChloroformSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

(S)-4-Benzyloxycarbonylamino-2-hydroxybutyric acid (5.25 g, 20.7 mmol) synthesized according to the report of Kawaguchi et al. (Journal of Antibiotics, Vol. 25, pp. 695-708 (1972)) was dissolved in 60 mL of N,N-dimethylformamide. Barium oxide (15.9 g, 103.7 mmol) was added under an ice bath. After the elapse of 2 min from the addition of barium oxide, barium hydroxide octahydrate (13.4 g, 42.5 mmol) was added thereto under an ice bath. After 10 min, benzyl bromide (7.5 mL, 63.1 mmol) was added thereto under an ice bath. After 5 min, the reaction solution was returned to room temperature and was vigorously stirred. After 1.5 hr, the completion of the reaction was confirmed by TLC (developing solvent system=chloroform:ethyl acetate:acetic acid=10:5:1), and water (0.5 mL) was added thereto under an ice bath. The mixture was diluted with chloroform (165 ml), and 4 N HCl (70 mL) was added thereto. Further, water (25 mL) was added followed by separation. The water layer was extracted with chloroform (50 mL). The organic layer and the extracted organic layer were combined and were washed with a saturated aqueous NaCl solution. The washed solution was dried over magnesium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by column chromatography on silica gel (silica gel 60, neutral spheres, 160 g) (chloroform:ethyl acetate=4:1→chloroform:methanol=10:1→chloroform:methanol:acetic acid=10:1:0.1 (600 mL)) to give (S)-2-benzyloxy-4-benzyloxycarbonylaminobutyrylic acid (2.86 g, 8.34 mmol).

Workup

  1. additionwas added
  2. waitAfter 5 min
  3. customwas returned to room temperature
  4. waitAfter 1.5 hr
  5. additionwas added
  6. additionwas added
  7. customfollowed by separation
  8. extractionThe water layer was extracted with chloroform (50 mL)
  9. washwere washed with a saturated aqueous NaCl solution
  10. dry with materialThe washed solution was dried over magnesium sulfate
  11. customThe solvent was removed by distillation under the reduced pressure
  12. customthe residue was purified by column chromatography on silica gel (silica gel 60, neutral spheres, 160 g) (chloroform:ethyl acetate=4:1→chloroform:methanol=10:1→chloroform:methanol:acetic acid=10:1:0.1 (600 mL))
  13. customto give (S)-2-benzyloxy-4-benzyloxycarbonylaminobutyrylic acid (2.86 g, 8.34 mmol)

Sources & evidence

ORD record
ord-d74e7d166ce04bb984daf6c1ecd3864e
Source dataset
uspto-grants-2016_02
Patent number
US09260465B2

Reaction notes

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