Reacción #1175727

Ecuación de reacción

methyl sarcosinate hydrochloride

triethylamine

1-hydroxybenzotriazole

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide

2-bromo-6-methoxy-5-trifluoromethyl-1-naphthoic acid

triethylamine

→

product

Rendimiento 75.0%

N-[[2-Bromo-6-methoxy-5-(trifluoromethyl)-1-naphthalenyl]carbonyl]-N-methylglycine, Methyl Ester

Rendimiento 75.0%

Disolventes

DMF

water

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.DISSOLUTIONDissolution
2. 2
   workup.WAITAfter 1 hour
3. 3
   workup.ADDITIONwas added to the reaction mixture
4. 4
   ExtracciónThe aqueous phase was extracted with ether (4×250 mL)
5. 5
   Lavadowashed with 0.5N sodium hydroxide solution (1×200 mL) and saturated aqueous sodium chloride (1×200 mL)
6. 6
   SecadoThe ether phase was dried with magnesium sulfate
7. 7
   Otrothe ether was removed
8. 8
   Otrochromatographed (3:2 to 2:3 petroleum ether:ethyl acetate eluent gradient, silica)
9. 9
   Otrothen reflash chromatographed (99:1 to 9:1 methylene chloride:acetonitrile eluent gradient, silica)

Procedimiento

1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide (7.91 g, 1.2 eq) was added to a stirred solution of 2-bromo-6-methoxy-5-trifluoromethyl-1-naphthoic acid, prepared by the process of Example 14, Step 2 (12.00 g, 34.4 mmol) and 1-hydroxybenzotriazole (6.97 g, 1.5 eq) in anhydrous DMF (105 mL) at room temperature under a dry nitrogen atmosphere. Dissolution occurred after 20 minutes. After 1 hour, a suspension of methyl sarcosinate hydrochloride (9.56 g, 2.0 eq) in anhydrous DMF (60 mL) was added to the reaction mixture followed by triethylamine (15.8 mL, 3.3 eq). After 21/2 hours, more triethylamine (4.8 mL, 1.0 eq) was added. The reaction was diluted with water (1.6 L) after 181/2 hours. The aqueous phase was extracted with ether (4×250 mL). The extracts were combined and washed with 0.5N sodium hydroxide solution (1×200 mL) and saturated aqueous sodium chloride (1×200 mL). The ether phase was dried with magnesium sulfate and the ether was removed. The crude product was flash chromatographed (3:2 to 2:3 petroleum ether:ethyl acetate eluent gradient, silica) then reflash chromatographed (99:1 to 9:1 methylene chloride:acetonitrile eluent gradient, silica) to provide the product as a white foam (11.16 g, 75%).

Fuente