Reaktion #6464

Reaktionsgleichung

diphenylphosphoryl azide

2d

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

triethylamine

4-ethylpiperidine

→

3d

Ausbeute 91.1%

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

Ausbeute 91.1%

Lösungsmittel

dimethylformamide

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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.

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