Reacción #6464

Ecuación de reacción

diphenylphosphoryl azide

2d

2-[[[5-(dimethylamino)-1-naphthalenyl]sulfonyl]amino]-5-[[(phenylmethoxy)carbonyl]amino]pentanoic acid

triethylamine

4-ethylpiperidine

→

3d

Rendimiento 91.1%

phenylmethyl [4-[ [[5-(dimethylamino)-1-naphthalenyl]sulfonyl]amino]-5-[4-ethyl-1-piperidinyl]-5-oxopentyl]carbamate

Rendimiento 91.1%

Disolventes

dimethylformamide

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas partitioned between ether (150 mL) and water (80 mL)
2. 2
   OtroThe ethereal layer was separated
3. 3
   Extracciónthe aqueous layer was extracted four additional times with ether (80 mL)
4. 4
   LavadoThe combined ethereal extracts were then washed with saturated sodium bicarbonate solution and brine
5. 5
   Otroto drying
6. 6
   Concentración(Na2SO4) and solvent concentration
7. 7
   OtroPurification of the combined residues by HPLC on silica gel (elution with 50% ethyl acetate in hexane)

Procedimiento

To a cold (0° C.), nitrogen-blanketed mixture of 2d (48.90 g, 0.098 mol), triethylamine (25.0 mL, 0.18 mol) and 4-ethylpiperidine (20.0 g, 0.18 mol) in anhydrous dimethylformamide (160 mL) was added dropwise diphenylphosphoryl azide (21.1 mL, 0.098 mol). The mixture was stirred at about 0° C. for about 1 hour and at ambient temperature for about 2 hours before it was partitioned between ether (150 mL) and water (80 mL). The ethereal layer was separated and the aqueous layer was extracted four additional times with ether (80 mL). The combined ethereal extracts were then washed with saturated sodium bicarbonate solution and brine prior to drying (Na2SO4) and solvent concentration. Two identical reactions were performed in tandem. Purification of the combined residues by HPLC on silica gel (elution with 50% ethyl acetate in hexane) furnished 53.09 g (45%) of 3d as a yellow foam, m.p. 56°-62° C. (dec.); 1H NMR (CDCl3) δ 8.47 (d, 1H), 8.30 (t, 1H), 8.16 (d, 1H), 7.58 (m, 1H), 7.56-7.36 (m, 6H), 7.15 (d, 1H), 6.17-5.96 (dd, 1H), 5.10 (s, 2H), 4.75-4.62 (bm, 1H), 4.10-3.91 (bm, 2H), 3.42-3.30 (bm, 1H), 3.16-2.92 (bm, 2H), 2.85-2.83 (d, 6H), 2.68-2.41 (dt, 1H), 2.24-1.97 (m, 1H), 1.57-0.76 (m, 3 H), 0.16-0.08 (m, 1H); 13C NMR (CDCl3) ppm 168.50, 156.40, 151.62, 136.50, 135.00, 134.70, 130.56, 130.44, 129.80, 129.35, 129.18, 128.50, 128.41, 128.07, 128.00, 123.01, 122.93, 119.33, 115.58, 115.47, 66.60, 52.29, 52.19, 45.70, 45.43, 45.37, 45.13, 42.02, 42.21, 40.35, 40.18, 37.48, 37.34, 32.17, 31.92, 31.06, 30.79, 30.65, 29.67, 28.77, 28.58, 25.12, 11.08; IR (KBR, cm-1) 33,50 2975, 2975, 2950, 1725, 1650, 1550, 1475, 1350, 1275, 1180, 1160; MS m/z (MH+) 595.

Fuente