Reaktion #158062

Reaktionsgleichung

(R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate

3-chlorophenylboronic acid

Na2CO3

→

(R)-ethyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate

Ausbeute 62.9%

Lösungsmittel

1,2-dimethoxyethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture is cooled to room temperature
2. 2
   Sonstigequenched with brine
3. 3
   SonstigeThe two phases are separated
4. 4
   ExtraktionThe mixture is extracted twice with ethyl acetate from the aqueous layer
5. 5
   WaschenThe combined organic layer is washed with brine
6. 6
   Trocknendried over MgSO4
7. 7
   Filtrationfiltered
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   SonstigeThe obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30)

Vorschrift

A mixture of (R)-ethyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (4.89 g, 12.66 mmol), 3-chlorophenylboronic acid (2.97 g, 18.99 mmol), Pd(PPh3)4 (1.463 g, 1.266 mmol) and 2 M aqueous Na2CO3 (12.66 ml, 25.3 mmol) in 1,2-dimethoxyethane (100 ml) is allowed to stir at 95° C. under nitrogen for 3 hours. The reaction mixture is cooled to room temperature and quenched with brine. The two phases are separated. The mixture is extracted twice with ethyl acetate from the aqueous layer. The combined organic layer is washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by silica gel flash column chromatography (heptane/EtOAc=100:0 to 70:30) to give (R)-ethyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate (3.33 g); HPLC retention time=1.44 minutes (condition B); MS (ES+)=318.26 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.2 Hz, 3 H) 1.41 (s, 9 H) 2.47 (A of ABX, Jab=15.8 Hz, Jax=5.9 Hz, 1 H) 2.52 (B of ABX, Jab=15.8 Hz, Jbx=5.4 Hz, 1 H) 2.83-2.89 (m, 1 H) 2.95-3.00 (m, 1 H) 4.17 (q, J=7.2 Hz, 2 H) 4.18 (br s, 1 H) 5.07 (br s, 1 H) 7.26-7.37 (m, 4 H) 7.43-7.51 (m, 3 H) 7.55 (br t, J=1.8 Hz, 1 H).

Quelle