Réaction #158042

Équation de réaction

(R)-tert-butyl 4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate

HCl

1,4-dioxane

succinic anhydride

DIPEA

→

(R)-4-(1-(biphenyl-4-yl)-4-tert-butoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid

Rendement 36.1%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   Concentrationconcentrated under reduced pressure
2. 2
   workup.STIRRINGto stir at room temperature for 14 hours
3. 3
   Concentrationconcentrated under reduced pressure
4. 4
   AutreThe obtained residue is purified by RP-HPLC (SunFire C-18, H2O (0.1% TFA)/CH3CN)

Mode opératoire

To (R)-tert-butyl 4-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)butanoate (26.4 mg, 0.064 mmol) is added 4M HCl in 1,4-dioxane (0.321 ml, 1.283 mmol) at room temperature. The reaction mixture is stirred for 45 minutes and concentrated under reduced pressure. To a solution of the obtained residue in dichloromethane (0.4 mL) is added succinic anhydride (7.70 mg, 0.077 mmol) and DIPEA (0.013 mL, 0.077 mmol). The reaction mixture is allowed to stir at room temperature for 14 hours and concentrated under reduced pressure. The obtained residue is purified by RP-HPLC (SunFire C-18, H2O (0.1% TFA)/CH3CN) to give (R)-4-(1-(biphenyl-4-yl)-4-tert-butoxy-4-oxobutan-2-ylamino)-4-oxobutanoic acid (9.5 mg). HPLC retention time=1.70 minutes (condition A); MS (ES+)=412.1 (m+1); 356.0 (m-tBu+2; 100%); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.48 (s, 9 H) 2.36-2.51 (m, 4 H) 2.64-2.67 (m, 2 H) 2.87 (A of ABX, Jab=13.5 Hz, Jax=5.7 Hz, 1 H), 2.97 (Jab=13.5 Hz, Jbx=6.2 Hz, 1 H) 7.24-7.26 (m, 2 H) 7.31-7.35 (m, 1 H) 7.43 (t, J=7.75 Hz, 2 H) 7.53(d, J=8.0 Hz, 2 H) 7.57 (d, J=7.6 HZ, 2 H).

Source