Ethanol → (S)-4-bromo-3-methyl-butyric acid ethyl ester

HRID 1096182Notes

Reaction equation

HRID 1096182 reaction equation
[C:1]([Br:4])(=O)[CH3:2].C[C@@H:6]1[CH2:10][O:9][C:8](=[O:11])[CH2:7]1.[CH3:12]CO>>[CH2:10]([O:9][C:8](=[O:11])[CH2:7][C@H:2]([CH3:12])[CH2:1][Br:4])[CH3:6]

Participants

4

Reactant 3

HCID 702Ethanol2×HCID 10482Acetyl bromideHCID 11115993(4S)-Dihydro-4-methyl-2(3H)-furanone

Product 1

HCID 11085055(S)-4-bromo-3-methyl-butyric acid ethyl ester

Procedure

To EtOH (55 ml) cooled to 0° C. was added acetyl bromide (41 ml, 0.6 mol) dropwise, followed by a solution of (S)-4-methyl-dihydro-furan-2-one (Tetrahedron 1983, 39, 3107; 18.6 g, 0.2 mol) in EtOH (20 ml). The ice bath was removed and the reaction allowed to reach RT. After 2 h of stirring the reaction was concentrated, the residue redissolved in CH2Cl2, washed with sat. aq. NaHCO3 solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quant). This was redissolved in EtOH (100 ml), cooled to 0° C. and N-benzylglycine ethyl ester (28.2 g, 0.14 mol) and triethylamine (22.4 ml, 0.16 mmol) were added. The reaction was then warmed to 75° C. for 4 d after which time the reaction was concentrated, the residue redissolved in CH2Cl2, washed with sat. aq. NaHCO3 solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (EtOAc/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+.

Workup

  1. customThe ice bath was removed
  2. customto reach RT
  3. concentrationwas concentrated
  4. dissolutionthe residue redissolved in CH2Cl2
  5. washwashed with sat. aq. NaHCO3 solution
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-5c3a1feb09684acaa6d95d5ff64c16ec
Source dataset
uspto-grants-2012_03
Patent number
US08138175B2

Reaction notes

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