2,4,6-Tri-t-butyl-1-bromobenzene → Racemic 3-{4-[1-(2,4,6-tri-t-butyl-phenoxy)-5,5,5-trifluoro-pentyl]-benzoylamino}-propionic acid methyl ester

HRID 1914351Notes

Reaction equation

HRID 1914351 reaction equation
[CH3:1][O:2][C:3](=[O:39])[CH2:4][CH2:5][NH:6][C:7](=[O:38])[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([O:22]C2C=CC(B3OC(C)(C)C(C)(C)O3)=CC=2)[CH2:15][CH2:16][CH2:17][C:18]([F:21])([F:20])[F:19])=[CH:10][CH:9]=1.Br[C:41]1[C:46]([C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:45][C:44]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:43][C:42]=1[C:55]([CH3:58])([CH3:57])[CH3:56].[F-].[K+]>C1(C)C=CC=CC=1>[CH3:1][O:2][C:3](=[O:39])[CH2:4][CH2:5][NH:6][C:7](=[O:38])[C:8]1[CH:13]=[CH:12][C:11]([CH:14]([O:22][C:41]2[C:46]([C:47]([CH3:50])([CH3:49])[CH3:48])=[CH:45][C:44]([C:51]([CH3:54])([CH3:53])[CH3:52])=[CH:43][C:42]=2[C:55]([CH3:58])([CH3:57])[CH3:56])[CH2:15][CH2:16][CH2:17][C:18]([F:20])([F:21])[F:19])=[CH:10][CH:9]=1

Participants

5

Reactant 3

HCID 1380892,4,6-Tri-t-butyl-1-bromobenzeneHCID 522689Potassium FluorideHCID 671534183-(4-{5,5,5-Trifluoro-1-[4-(4,4,5,5-tetramethyl[1,3,2]dioxaborolan-2-yl)-phenoxy]-pentyl}-benzoylamino)-propionic acid methyl ester

Product 1

HCID 67153635Racemic 3-{4-[1-(2,4,6-tri-t-butyl-phenoxy)-5,5,5-trifluoro-pentyl]-benzoylamino}-propionic acid methyl ester

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of racemic 3-(4-{5,5,5-Trifluoro-1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-pentyl}-benzoylamino)-propionic acid methyl ester (0.300 g, 0.550 mmol) in toluene (3.0 mL) is added palladium tetrakis triphenylphosphine (0.0316 g, 0.030 mmol), 2-bromo-1,3,5-tri-tert-butyl-benzene (0.353 g, 1.09 mmol), and potassium fluoride (0.063 g, 1.09 mmol). The reaction is purged with nitrogen three times and heated to reflux under nitrogen. At reflux, water (1.0 mL) is added to the reaction and the reaction is allowed to reflux under nitrogen. The reaction is monitored by HPLC, and upon completion, allowed to cool to room temperature. The reaction is diluted with ethyl acetate and celite is added, followed by water. This mixture is then filtered through a pad of celite. The solution is poured into a separatory funnel and the organic layer is washed with water and brine. The organic layer is dried over anhydrous sodium sulfate and concentrated. The product is purified by flash column chromatography (0.333 g, 0.500 mmol).

Workup

  1. customThe reaction is purged with nitrogen three times
  2. temperatureheated
  3. temperatureto reflux under nitrogen
  4. temperatureAt reflux
  5. additionwater (1.0 mL) is added to the reaction
  6. temperatureto reflux under nitrogen
  7. additionThe reaction is diluted with ethyl acetate and celite
  8. additionis added
  9. filtrationThis mixture is then filtered through a pad of celite
  10. additionThe solution is poured into a separatory funnel
  11. washthe organic layer is washed with water and brine
  12. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  13. concentrationconcentrated
  14. customThe product is purified by flash column chromatography (0.333 g, 0.500 mmol)

Sources & evidence

ORD record
ord-3e734c59b84a4b5b9fc6b5972c45cde3
Source dataset
uspto-grants-2013_12
Patent number
US08609892B2

Reaction notes

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