Reaction #3879

Reaction equation

N-methylmorpholine

t-butoxycarbonylphenylalanine

N-methylmorpholine

methyl 5-aminopentanoate hydrochloride

isobutylchloroformate

→

title compound

Yield 96.2%

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

Yield 96.2%

Solvents

dimethylformamide

Conditions

Workup

1. 1
   TemperatureAfter warming
2. 2
   Otherat ca. -15°
3. 3
   Otherfor about ten minutes
4. 4
   Otherwas recooled to ca. -39°
5. 5
   OtherSolvent and other volatiles were removed by concentration in vacuo
6. 6
   OtherThe residue was triturated with ethyl acetate, which
7. 7
   Washwas then washed successively with water, 0.5M potassium bisulfate, water
8. 8
   Dryingagain with 0.5M potassium bisulfate, and then dried over magnesium sulfate
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated to a white solid
11. 11
    OtherAfter collection
12. 12
    Washthe white solid was washed thoroughly with Skellysolve B

Procedure

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.

Source