Reaktion #1145564

Reaktionsgleichung

3-bromo-4-(methoxycarbonyl)benzoic acid

O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate

3-hydroxybenzylamine hydrochloride salt

3-hydroxybenzylamine hydrochloride

1-hydroxybenzotriazole

Diisopropylethylamine

→

2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid methyl ester

Ausbeute 73.3%

Lösungsmittel

N,N-dimethylformamide

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITat room temperature for 4 h
2. 2
   Einengenit was concentrated in vacuo (˜1 mm)
3. 3
   Sonstigeto remove most of the N,N-dimethylformamide
4. 4
   SonstigeThe residue was partitioned between ethyl acetate and 1N hydrochloric acid solution (200 mL each)
5. 5
   WaschenThe ethyl acetate layer was washed with 1N hydrochloric acid solution (2×100 mL)
6. 6
   Extraktionthe combined aqueous layers were extracted with ethyl acetate (50 mL)
7. 7
   WaschenThe combined ethyl acetate layers were washed with saturated sodium bicarbonate solution (2×100 mL) and brine
8. 8
   Trocknendried (MgSO4)
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated under reduced pressure
11. 11
    SonstigeThe solid residue was crystallized from hot ethyl acetate (˜60 mL) and hexanes (15 mL)

Vorschrift

Diisopropylethylamine (8.4 mL, 48.2 mmol) was added dropwise to a cooled (˜0° C.) solution of with 3-bromo-4-(methoxycarbonyl)benzoic acid (Example 76; 5.00 g, 19.3 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (7.31 g, 19.3 mmol), 3-hydroxybenzylamine hydrochloride salt (Example 69; 3.37 g, 21.2 mmol) and 1-hydroxybenzotriazole (2.6 g, 19.2 mmol) in N,N-dimethylformamide (50 mL). After the solution was allowed to stir at ˜0° C. for 1 h, then at room temperature for 4 h, it was concentrated in vacuo (˜1 mm) to remove most of the N,N-dimethylformamide. The residue was partitioned between ethyl acetate and 1N hydrochloric acid solution (200 mL each). The ethyl acetate layer was washed with 1N hydrochloric acid solution (2×100 mL) and the combined aqueous layers were extracted with ethyl acetate (50 mL). The combined ethyl acetate layers were washed with saturated sodium bicarbonate solution (2×100 mL) and brine, then dried (MgSO4), filtered and evaporated under reduced pressure. The solid residue was crystallized from hot ethyl acetate (˜60 mL) and hexanes (15 mL) to give 2-bromo-4-[[(3-hydroxybenzyl)amino]carbonyl]benzoic acid methyl ester (5.15 g, 73% yield) as colorless crystals.

Quelle