Chlorotrimethylsilane → Methyl 3-{[methyl(propyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoate

HRID 732546Notes

Reaction equation

HRID 732546 reaction equation
BrCCBr.Cl[Si](C)(C)C.Br[C:11]1[S:12][CH:13]=[CH:14][N:15]=1.[CH3:16][O:17][C:18](=[O:33])[C:19]1[CH:31]=[C:30](I)[CH:29]=[C:21]([C:22]([N:24]([CH3:28])[CH2:25][CH2:26][CH3:27])=[O:23])[CH:20]=1>C1COCC1.[Zn].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:16][O:17][C:18](=[O:33])[C:19]1[CH:31]=[C:30]([C:11]2[S:12][CH:13]=[CH:14][N:15]=2)[CH:29]=[C:21]([C:22]([N:24]([CH3:28])[CH2:25][CH2:26][CH3:27])=[O:23])[CH:20]=1

Participants

8

Reactant 4

HCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 764302-BromothiazoleHCID 21086185Methyl 3-iodo-5-{[methyl(propyl)amino]carbonyl}benzoate

Product 1

HCID 21086191Methyl 3-{[methyl(propyl)amino]carbonyl}-5-(1,3-thiazol-2-yl)benzoateYield 95%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a previously nitrogen-flushed vessel, add zinc dust (<10 microns, 0.196 g, 3 mmol) and 1,2-dibromoethane (0.023 mL, 0.27 mmol) to THF (0.5 mL). Heat the solution until bubbles appear. Repeat the heating twice and cool to room temperature. Add chlorotrimethylsilane (15 μL) and 2-bromothiazole (90 μL, 1 mmol) in THF (0.4 mL). Stir at room temperature for 15 min. Add 5-iodo-N-methyl-N-propyl-isophthalamic acid methyl ester (541 mg, 1.5 mmol), tetrakis(triphenylphosphine)palladium (0) (15 mg) and flush the mixture with nitrogen again before heating to reflux for 10 h. Cool to room temperature, concentrate and purify (silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes) to give the title compound (95%).

Workup

  1. customTo a previously nitrogen-flushed vessel
  2. temperatureHeat the solution until bubbles
  3. temperaturebefore heating
  4. temperatureto reflux for 10 h
  5. temperatureCool to room temperature
  6. concentrationconcentrate
  7. custompurify
  8. wash(silica gel chromatography, eluting with 0:100 to 40:60 ethyl acetate:hexanes)

Sources & evidence

ORD record
ord-23c56aa255d14dcfbe6a2e1beec16bc7
Source dataset
uspto-grants-2009_09
Patent number
US07585885B2

Reaction notes

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