1,4-Dibromobenzene → methyl (S)-3-(4-bromophenyl)-2-hydroxypropionate

HRID 1864544Notes

Reaction equation

HRID 1864544 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:12]=[CH:11][C:10]([Br:13])=[CH:9][CH:8]=1.[Cu](C#N)C#N.[C:19]([O:24][CH3:25])(=[O:23])[C@H:20]1[O:22][CH2:21]1.[Cl-].[NH4+]>CCCCC>[Br:13][C:10]1[CH:11]=[CH:12][C:7]([CH2:21][C@H:20]([OH:22])[C:19]([O:24][CH3:25])=[O:23])=[CH:8][CH:9]=1

Participants

7

Reactant 5

HCID 78041,4-DibromobenzeneHCID 25517Ammonium ChlorideHCID 10942355Methyl (2S)-2-oxiranecarboxylateHCID 178418260HCID 178418260, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 39359925methyl (S)-3-(4-bromophenyl)-2-hydroxypropionateYield 133.4%

Reagents, catalysts & solvents 1

HCID 8003PentaneSolvent

Conditions

Temperature
-30 °C

Procedure

100 ml (170 mmol) of a 1.7 M solution of tert-butyllithium in pentane are added dropwise to a solution of 48 g (204 mmol) of 1,4-dibromobenzene in 160 ml of tert-butyl dimethyl ether, cooled to −30° C., followed by addition of 7.3 g (82 mmol) of copper cyanide. The reaction medium is stirred for 15 minutes and a solution of 6 ml (68 mmol) of (S)-methyl glycidate in 10 ml of tert-butyl dimethyl ether is then added. After stirring for 20 minutes at −30° C., the reaction medium is hydrolysed with 150 ml of saturated aqueous ammonium chloride solution and extracted with ethyl acetate. The organic phase is washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and evaporated. The residue obtained is purified by chromatography on a column of silica eluted with heptane, and the polarity is then increased up to a 6/4 heptane/ethyl acetate mixture. 23.5 g (44%) of methyl 3-(4-bromophenyl)-2(S)-hydroxypropanoate are obtained.

Workup

  1. stirringAfter stirring for 20 minutes at −30° C.
  2. extractionextracted with ethyl acetate
  3. washThe organic phase is washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue obtained
  8. customis purified by chromatography on a column of silica
  9. washeluted with heptane
  10. temperaturethe polarity is then increased up to a 6/4 heptane/ethyl acetate mixture

Sources & evidence

ORD record
ord-f8c3e5442aa64e71abe78d6d2bb497f7
Source dataset
uspto-grants-2009_12
Patent number
US07625914B2

Reaction notes

Loading…