Reaktion #2178684

Reaktionsgleichung

PPh3

diethyl azodicarboxylate

ethyl glycolate

sodium hydride

2-oxo-cyclohexanecarbonitrile

→

desired product

Ausbeute 42.0%

3-Amino-4,5,6,7-tetrahydro-benzofuran-2-carboxylic acid ethyl ester

Ausbeute 42.0%

Lösungsmittel

THF

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigeat 0° C.
2. 2
   FiltrationFiltration and concentration
3. 3
   Sonstigeafforded the uncyclized intermediate, which
4. 4
   TemperaturThe reaction mixture was heated to 40° C. for 12 h
5. 5
   SonstigeThe reaction was quenched with satd
6. 6
   Extraktionaq. NH4Cl (5 mL) and the mixture was extracted with EtOAc (3×50 mL)
7. 7
   TrocknenThe combined organic layers were dried (by using, for example, Na2SO4)
8. 8
   Einengenconcentrated
9. 9
   SonstigePurification by FCC (50% EtOAc/hexanes)

Vorschrift

A solution of resin bound PPh3 (Polymer Laboratories, 1.48 mmol/g, 150-300 μM; 3.8 g, 5.7 mmol) in THF (35 mL) at 0° C. was treated with diethyl azodicarboxylate (40% wt. in hexane; 2.60 mL, 5.7 mmol), ethyl glycolate (0.54 mL, 5.7 mmol) and a solution of 2-oxo-cyclohexanecarbonitrile (0.5 g, 4.1 mmol) in THF (10 mL). The reaction mixture warmed to rt over 12 h. Filtration and concentration afforded the uncyclized intermediate, which was dissolved in THF (25 mL) and added drop-wise to a slurry of sodium hydride (95%; 0.29 g, 11.4 mmol) in THF (10 mL) at 0° C. The reaction mixture was heated to 40° C. for 12 h. The reaction was quenched with satd. aq. NH4Cl (5 mL) and the mixture was extracted with EtOAc (3×50 mL). The combined organic layers were dried (by using, for example, Na2SO4) and concentrated. Purification by FCC (50% EtOAc/hexanes) afforded the desired product as a pale yellow solid (0.36 g). MS: 210.2. 1H NMR (400 MHz, CD3OD) δ ppm 4.26 (q, J=7.1, Hz, 2H), 2.55-2.47 (m, 2H), 2.35-2.28 (m, 2H), 1.90-1.79 (m, 2H), 1.79-1.71 (m, 2H), 1.33 (t, J=7.1, Hz, 3H).

Quelle