Reaktion #67547

Reaktionsgleichung

84

N-(9-fluorenylmethoxycarbonyl)-O-(4,4-bis(diethylphosphoryl)butyl)-L-tyrosine

HCl

→

liquid 85

Ausbeute 97.8%

O-(4,4-bis(diethylphosphoryl)butyl)-L-tyrosine

Ausbeute 97.8%

Lösungsmittel

water

piperidine DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Waschenwas washed with diethyl ether (2×)
2. 2
   workup.ADDITIONthe pH was readjusted to ˜10 by the addition of 1N NaOH
3. 3
   ExtraktionThe product was extracted with ethyl acetate (3×)
4. 4
   Waschenwashed with saturated aqueous NaCl
5. 5
   Trocknendried over Na2SO4
6. 6
   SonstigeThe crude material was purified by silica gel chromatography (0 to 10% methanol in CH2Cl2 over 10 column volumes

Vorschrift

A solution of 84 (490 mg, 0.622 mmol) in piperidine/DMF (1:1, 4 mL) was stirred at room temperature for 45 min. After diluting with water and adjusting the pH to ˜3 by the addition of 1N HCl the aqueous layer was washed with diethyl ether (2×) then the pH was readjusted to ˜10 by the addition of 1N NaOH. The product was extracted with ethyl acetate (3×) washed with saturated aqueous NaCl and dried over Na2SO4. The crude material was purified by silica gel chromatography (0 to 10% methanol in CH2Cl2 over 10 column volumes then 10 to 20% over 5 column volumes) using a Biotage Horizon™ apparatus resulting in the colourless liquid 85 (271 mg, 77%): 1H NMR (400 MHz, CDCl3) δ 1.33 (t, J=7.1, 6H), 1.34 (t, J=7.1, 6H), 1.43 (s, 9H), 2.04-2.17 (m, 4H), 2.37 (tt, J=5.8, 24.1, 1H), 2.77 (dd, J=7.6, 13.7, 1H), 2.97 (dd, J=5.5, 13.7, 1H), 3.55 (dd, J=5.5, 7.6, 1H), 3.94 (t, J=5.8, 2H), 4.14-4.23 (m, 8H), 6.78 (d, J=8.6, 2H), 7.10 (d, J=8.6, 2H): 31P (162 MHz, CDCl3) δ 24.76 (s, 2P).

Quelle