Potassium Carbonate → Methyl 4-(4-tert-butylthiazol-2-yl)-3-methylbenzoate

HRID 531252Notes

Reaction equation

HRID 531252 reaction equation
Br[C:2]1[S:3][CH:4]=[C:5]([C:7]([CH3:10])([CH3:9])[CH3:8])[N:6]=1.[CH3:11][C:12]1[CH:13]=[C:14]([CH:19]=[CH:20][C:21]=1B1OC(C)(C)C(C)(C)O1)[C:15]([O:17][CH3:18])=[O:16].C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[C:7]([C:5]1[N:6]=[C:2]([C:21]2[CH:20]=[CH:19][C:14]([C:15]([O:17][CH3:18])=[O:16])=[CH:13][C:12]=2[CH3:11])[S:3][CH:4]=1)([CH3:10])([CH3:9])[CH3:8]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 110870242-Methyl-4-methoxycarbonylphenylboronic acid, pinacol esterHCID 422818732-Bromo-4-tert-butyl-1,3-thiazole

Product 1

HCID 90009157Methyl 4-(4-tert-butylthiazol-2-yl)-3-methylbenzoateYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a suspension of 2-bromo-4-(1,1-dimethylethyl)thiazole (6 g, 27.3 mmol), methyl 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (9.78 g, 35.4 mmol), and potassium carbonate (11.30 g, 82 mmol) in 1,4-dioxane (20 mL) and water (5 mL), was added 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.113 g, 1.363 mmol). It was degassed and refilled with nitrogen, and was heated to reflux for 1 hour to see complete conversion of the 2-bromothiazole, by LCMS. It was distributed between water (50 mL) and ethyl acetate (200 mL). The organic layer was collected, dried over sodium sulfate, filtered and the filtrate concentrated. The crude isolate was purified on silica gel, eluting with 30% of ethyl acetate in hexanes, to get methyl 4-(4-tert-butylthiazol-2-yl)-3-methylbenzoate as a white solid (7.3 g, 93% yield). LCMS (M+H)+: 290.1. 1H NMR (CDCl3, 500 MHz): δ 8.00 (s, 1H), 7.93 (d, J=8.5 Hz, 1H), 7.83 (d, J=8.5 Hz, 1H), 7.02 (s, 1H), 3.97 (s, 3H), 2.70 (s, 3H), 1.43 (s, 9H).

Workup

  1. additionwas added 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (1.113 g, 1.363 mmol)
  2. customIt was degassed
  3. additionrefilled with nitrogen
  4. temperaturewas heated
  5. temperatureto reflux for 1 hour
  6. customThe organic layer was collected
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate concentrated
  10. customThe crude isolate
  11. customwas purified on silica gel
  12. washeluting with 30% of ethyl acetate in hexanes

Sources & evidence

ORD record
ord-01edc7718ceb47b0b5aaba50758ee35b
Source dataset
uspto-grants-2016_05
Patent number
US09353101B2

Reaction notes

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