반응 #158063

반응 방정식

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

3-chlorophenylboronic acid

→

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

수율 48.1%

용매

brine

EtOAc

Toluene

반응 조건

후처리

1. 1
   온도The reaction mixture is cooled to ambient temperature
2. 2
   추출The products are extracted twice with EtOAc
3. 3
   세척washed with brine
4. 4
   건조dried over MgSO4
5. 5
   여과filtered
6. 6
   농축concentrated
7. 7
   기타The residue is purified by flash column chromatography on 90 g silica gel (eluent: heptane/EtOAc=100:0 to 65:35)

실험 절차

A suspension of give (R)-benzyl 4-(4-bromophenyl)-3-(tert-butoxycarbonylamino)butanoate (2.00 g, 4.46 mmol), 3-chlorophenylboronic acid (1.046 g, 6.69 mmol), Pd(PPh3)4 (0.515 g, 0.446 mmol) and Na2CO3aq (4.46 ml, 8.92 mmol) in Toluene (30 ml) is allowed to stir under nitrogen at 95° C. for 19 hr. The reaction mixture is cooled to ambient temperature, and diluted with brine and EtOAc. The products are extracted twice with EtOAc, washed with brine, dried over MgSO4, filtered, and concentrated. The residue is purified by flash column chromatography on 90 g silica gel (eluent: heptane/EtOAc=100:0 to 65:35) to give (R)-benzyl 3-(tert-butoxycarbonylamino)-4-(3′-chlorobiphenyl-4-yl)butanoate (1.03 g); HPLC retention time=1.74 minutes (condition B); MS (ES+)=380.2 (m-BOC+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.40 (s, 9 H) 2.52 (A of ABX, Jab=15.9 Hz, Jax=5.8 Hz, 1 H) 2.58 (B of ABX, Jab=15.9 Hz, Jbx=5.6 Hz, 1 H) 2.81-2.98 (m, 2 H) 4.19 (br s, 1 H) 5.07 (br d, 1 H) 5.12 (A of AB, J=12.3 Hz, 1 H) 5.17 (A of AB, J=12.3 Hz, 1 H) 7.20-7.22 (m, 2 H) 7.28-7.39 (m, 7 H) 7.42-7.47 (m, 3 H) 7.53-7.54 (m, 1 H).

출처