Reaktion #320813

Reaktionsgleichung

amino acid

2-amino-3-(3-indolyl)butanoic acid

sodium hydrogen carbonate

chloroformate

2-adamantyl chloroformate

methanol

→

2-(2-adamantyloxycarbonyl)amino-3-(3-indolyl) butanoic acid

Ausbeute 63.0%

2-(2-Adamantyloxycarbonyl)amino-3-(3-indolyl)butanoic acid

Ausbeute 63.0%

Lösungsmittel

sodium hydroxide

dichloromethane

dioxan

dioxan

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITION(2.29 mL) was added
2. 2
   workup.ADDITIONfollowed by dropwise addition
3. 3
   Sonstigethe dioxan was removed in vacuo
4. 4
   Sonstigethe residue partitioned between 10% citric acid and ethyl acetate
5. 5
   ExtraktionThe aqueous phase was extracted further with ethyl acetate
6. 6
   Trocknendried (MgSO4)
7. 7
   Sonstigeevaporated to dryness
8. 8
   SonstigeThe crude acid was purified by column chromatography on normal silica [hexane: ethyl acetate (3:20+0.5% acetic acid as eluant]

Vorschrift

Percent amino acid (75) (449 mg, 2.29 mmol) in 1N sodium hydroxide (2.29 mL) was added to sodium hydrogen carbonate (211 mg, 2.5 mmol). This mixture was cooled to 0° C. (ice bath), dioxan. (2.29 mL) was added, followed by dropwise addition with stirring of a solution of the chloroformate (76) (742 mg, 34.46 mmol) in dioxan (2.29 mL). When all the amino acid had gone (TLC SiO2 :4% methanol in dichloromethane), the dioxan was removed in vacuo and the residue partitioned between 10% citric acid and ethyl acetate. The aqueous phase was extracted further with ethyl acetate. The organic extracts were combined, dried (MgSO4), and evaporated to dryness. The crude acid was purified by column chromatography on normal silica [hexane: ethyl acetate (3:20+0.5% acetic acid as eluant] to give 2-(2-adamantyloxycarbonyl)amino-3-(3-indolyl) butanoic acid (77) (570 mg, 63%); δ H (300M Hz, d6 -DMSO), 1.34 (3H, d, J 8Jz. CH3), 1.68-2.00 (14H, m, adamantyl), 3.40-3.53 (1H, m, indCH(CH3)), 4.36 (1H, brt, CH(CO2H)), 4.59 (1H, s, adamantyl 2-H), 6.73 (1H, d, J 9 Hz, urethane NH), 6.96 (1H, t, J 7 Hz, indole 5-H), 7.06 m (1H, t, J 7 Hz, indole 6-H), 7.17 (1H, brs, indole 2-H), 7.33 (1H, d, J 8 Hz, indole 7-H), 7.60 (1H, d, J 8 Hz, indole 4-H), 10.83 (1H, s, indole NH)m, ca 12.6 (vbrs, CO2H).

Quelle