Ethanol → (S)-4-bromo-3-methyl-butyric acid ethyl ester
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.[CH2:12](O)C>>[CH2:10]([O:9][C:8](=[O:11])[CH2:7][C@H:2]([CH3:12])[CH2:1][Br:4])[CH3:6]Participants
Procedure
To ethanol (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 ethanol (20 ml). The ice bath was removed and the reaction allowed to reach room temperature. After 2 h of stirring the reaction was concentrated, the residue redissolved in dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated affording (S)-4-bromo-3-methyl-butyric acid ethyl ester (33.6 g, quant). This was redissolved in ethanol (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 dichloromethane, washed with saturated aq. sodium hydrogencarbonate solution, dried (Na2SO4) and concentrated. Purification by flash column chromatography (ethyl acetate/heptane 5:95) afforded the titled product as a light gold oil (20.3 g, 43%). MS (ISP)=322.2 (M+H)+.
Workup
- customThe ice bath was removed
- customto reach room temperature
- concentrationwas concentrated
- dissolutionthe residue redissolved in dichloromethane
- washwashed with saturated aq. sodium hydrogencarbonate solution
- dry with materialdried (Na2SO4)
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-3225ce87bb9e4581b6654c6a7a1616a8
- Source dataset
- uspto-grants-2011_11
- Patent number
- US08063042B2
Reaction notes
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