Reaktion #158065

Reaktionsgleichung

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

2,5-dichlorophenylboronic acid

Na2CO3

→

(R)-ethyl 3-(tert-butoxycarbonylamino)-4-(2′,5′-dichlorobiphenyl-4-yl)butanoate

Ausbeute 92.7%

Lösungsmittel

1,2-dimethoxyethane

brine

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture is cooled to room temperature
2. 2
   SonstigeThe two phases are separated
3. 3
   ExtraktionThe products are extracted twice with ethyl acetate (2×100 ml) from the aqueous layer
4. 4
   WaschenThe combined organic layer is washed with brine
5. 5
   Trocknendried over MgSO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   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 (1.005 g, 2.60 mmol), 2,5-dichlorophenylboronic acid (0.745 g, 3.90 mmol), Pd(PPh3)4 (0.301 g, 0.260 mmol) and 2 M aqueous Na2CO3 (2.60 ml, 5.20 mmol) in 1,2-dimethoxyethane (20 ml) is allowed to stir at 95° C. under nitrogen for 3 hours. The reaction mixture is cooled to room temperature and diluted with brine. The two phases are separated. The products are extracted twice with ethyl acetate (2×100 ml) 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-(2′,5′-dichlorobiphenyl-4-yl)butanoate (1.09 g); HPLC retention time=1.50 minutes (condition B); MS (ES+)=352.00 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.28 (t, J=7.1 Hz, 3 H) 1.41 (s, 9 H) 2.45-2.58 (m, 2 H) 2.85-3.00 (m, 2 H) 4.17 (t, J=7.1 Hz, 2 H) 4.20 (br s, 1 H) 5.06-5.08 (m, 1 H) 7.23-7.28 (m, 3 H) 7.31-7.40 (m, 4 H).

Quelle