Chlorotrimethylsilane → 2-Bromo-3-(3,4-dimethoxyphenyl)-propionic acid methyl ester

HRID 2292478Notes

Reaction equation

HRID 2292478 reaction equation
Cl[Si](C)(C)C.[CH3:6][O:7][C:8](=[O:21])[CH2:9][CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1.[Br:22]N1C(=O)CCC1=O>C1COCC1>[CH3:6][O:7][C:8](=[O:21])[CH:9]([Br:22])[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[C:13]([O:19][CH3:20])[CH:12]=1

Participants

5

Reactant 3

HCID 6397ChlorotrimethylsilaneHCID 67184N-bromobutanimideHCID 520347Methyl 3-(3,4-dimethoxyphenyl)propanoate

Product 1

HCID 105185152-Bromo-3-(3,4-dimethoxyphenyl)-propionic acid methyl esterYield 102.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

85.68 ml 1.6N butyllithium solution in hexane (0,136 mol) was admixed with 19.27 ml (0.136 mol) diisopropylamine at -10° C. under nitrogen. Afterwards the white suspension was stirred for 30 minutes at -10° C., admixed with 200 ml absolute tetrahydrofuran (abs. THF) and the lithium diisopropylamide solution obtained was cooled to -78° C. Subsequently a solution of 25.6 ml (0.2 mol) freshly distilled chlorotrimethylsilane in 20 ml abs. THF was quickly added, a solution of 24.5 g (0.109 mol) 3-(3,4-dimethoxyphenyl)-propionic acid methyl ester in 50 ml abs. THF was then added dropwise within 10 minutes and afterwards the reaction mixture was stirred for one hour at -78° C. Subsequently 22.6 g (0.127 mol) N-bromosuccinimide was added, the reaction mixture was allowed to reach room temperature (1 h) and it was stirred for a further 8 hours. After removing the precipitate that formed by filtration, the mother liquor was concentrated in a vacuum, the residue was taken up in 100 ml diethyl ether, the ether solution was washed with saturated sodium thiosulfate solution and dried over sodium sulfate. After removing the ether, 33.8 g 2-bromo-3-(3,4-dimethoxyphenyl)-propionic acid methyl ester was obtained as a light brown oil. 1H-NMR (CDCl3): δ=6.75 (m, 3H); 4.35 (dd, 1H); 3.85 (s, 3H); 3.83 (s, 3H); 3.7 (s, 3H); 3.4 (dd, 1H); 3.15 (dd, 1H).

Workup

  1. customto reach room temperature
  2. custom(1 h) and it
  3. stirringwas stirred for a further 8 hours
  4. customAfter removing the precipitate
  5. customthat formed by filtration
  6. concentrationthe mother liquor was concentrated in a vacuum
  7. washthe ether solution was washed with saturated sodium thiosulfate solution
  8. dry with materialdried over sodium sulfate
  9. customAfter removing the ether

Sources & evidence

ORD record
ord-856a3cad4de84a338d726fb9af1eaf0a
Source dataset
uspto-grants-1997_11
Patent number
US05683994

Reaction notes

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