Reacción #3879

Ecuación de reacción

N-methylmorpholine

t-butoxycarbonylphenylalanine

N-methylmorpholine

methyl 5-aminopentanoate hydrochloride

isobutylchloroformate

→

title compound

Rendimiento 96.2%

t-butoxycarbonyl-N-(5-methoxy-5-oxopentyl)-L-phenylalaninamide

Rendimiento 96.2%

Disolventes

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaAfter warming
2. 2
   Otroat ca. -15°
3. 3
   Otrofor about ten minutes
4. 4
   Otrowas recooled to ca. -39°
5. 5
   OtroSolvent and other volatiles were removed by concentration in vacuo
6. 6
   OtroThe residue was triturated with ethyl acetate, which
7. 7
   Lavadowas then washed successively with water, 0.5M potassium bisulfate, water
8. 8
   Secadoagain with 0.5M potassium bisulfate, and then dried over magnesium sulfate
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated to a white solid
11. 11
    OtroAfter collection
12. 12
    Lavadothe white solid was washed thoroughly with Skellysolve B

Procedimiento

To a cold (ca -30° ), stirred solution of 26.5 g (0.1 mole) of t-butoxycarbonylphenylalanine (BOC-Phe) and 11.2 g (0.1 mole) of N-methylmorpholine in 150 ml of dimethylformamide (DMF) was added dropwise 13.2 ml (0.1 mole) of isobutylchloroformate. After warming and then holding the temperature at ca. -15° for about ten minutes, the solution was recooled to ca. -39°. To the cold mixture was added additional N-methylmorpholine (12.3 ml, ca. 0.11 mole), followed by 18.5 g (0.11 mole) of methyl 5-aminopentanoate hydrochloride. The mixture was allowed to warm to room temperature and to stand overnight. Solvent and other volatiles were removed by concentration in vacuo. The residue was triturated with ethyl acetate, which was then washed successively with water, 0.5M potassium bisulfate, water, and again with 0.5M potassium bisulfate, and then dried over magnesium sulfate, filtered, and concentrated to a white solid. After collection, the white solid was washed thoroughly with Skellysolve B to give 36.4 g of the title compound, m.p. 98°-100°. Recrystallization from ethyl acetate/Skellysolve B afforded analytically pure crystals.

Fuente