Reaktion #59692

Reaktionsgleichung

4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid

Intermediate 21

4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid

DIPEA

HATU

2-Aminothiazole

→

4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-(thiazol-2-yl)-benzamide

Ausbeute 65.5%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGthe reaction stirred at room temperature for 18 hours
2. 2
   SonstigeThe solvent was evaporated under vacuum
3. 3
   Sonstigethe reaction partitioned between ethyl acetate (250 ml) and water (50 ml)
4. 4
   WaschenThe organic phase was washed with hydrochloric acid (2N, 50 ml) and aqueous sodium bicarbonate (1M, 50 ml)
5. 5
   Trocknendried (magnesium sulphate)
6. 6
   Sonstigethe solvent evaporated under vacuum
7. 7
   SonstigeThe residue was absorbed onto silica
8. 8
   Sonstigepurified by flash column chromatography
9. 9
   Wascheneluting with cyclohexane/ethyl acetate (4:1)
10. 10
    SonstigeThe solvent was evaporated from the product fractions under vacuum

Vorschrift

4-Methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzoic acid (Intermediate 21) (2.0 g, 7.63 mmol), DIPEA (4 ml, 22.89 mmol) and HATU (3.05 g, 8.02 mmol) were dissolved in DMF (20 ml) and stirred at room temperature for 15 mins. 2-Aminothiazole (801 mg, 8.01 mmol) was added and the reaction stirred at room temperature for 18 hours. The solvent was evaporated under vacuum and the reaction partitioned between ethyl acetate (250 ml) and water (50 ml). The organic phase was washed with hydrochloric acid (2N, 50 ml) and aqueous sodium bicarbonate (1M, 50 ml), then dried (magnesium sulphate) and the solvent evaporated under vacuum. The residue was absorbed onto silica and purified by flash column chromatography eluting with cyclohexane/ethyl acetate (4:1). The solvent was evaporated from the product fractions under vacuum to give 4-methyl-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-N-(thiazol-2-yl)-benzamide (1.72 g).

Quelle