Hydrochloric Acid → JNJ17156516
Reaction equation
C(OC(C([O:8][C:9](=[O:40])[C@H:10]([C:33]1[CH:34]=[C:35]([CH3:39])[CH:36]=[CH:37][CH:38]=1)[CH2:11][C:12]1[CH:16]=[C:15]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([Cl:24])[CH:18]=2)[N:14]([C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)[N:13]=1)C)=O)C.Cl>C(O)(=O)C>[Cl:24][C:19]1[CH:18]=[C:17]([C:15]2[N:14]([C:25]3[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=3)[N:13]=[C:12]([CH2:11][C@@H:10]([C:33]3[CH:34]=[C:35]([CH3:39])[CH:36]=[CH:37][CH:38]=3)[C:9]([OH:40])=[O:8])[CH:16]=2)[CH:22]=[CH:21][C:20]=1[Cl:23]Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 85 °C
Procedure
A 500-mL, 1-necked round-bottomed flask equipped with a magnetic stirring bar was charged with (S)-3-[5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazol-3-yl]-2-m-tolyl-propionic acid 1-ethoxycarbonyl-ethyl ester from Example 503 (18.5 g. 0.0318 mol), as a 4:1 mixture of regioisomers, in 150 mL of acetic acid. After the addition of 2 N HCl (25 mL), the reaction mixture was heated at 85° C. using an oil bath. After 4 h, when TLC indicated complete hydrolysis of the lactate ester, the heating source was removed and reaction flask cooled to rt. The mixture was concentrated under reduced pressure to remove most of acetic acid, and then 250 mL of EtOAc was added. The EtOAc solution was then washed with H2O (50 mL) and brine (50 mL), and then dried over Na2SO4. The solvents were removed under reduced pressure to obtain the crude acid as a brown oil (15 g, 98%). HPLC (Method E) indicated the product to be a mixture of 2 regioisomers in a 4:1 ratio. Chiral HPLC (Method S): Rt (S isomer)=8.1 min (enantiomeric ratio of 1:9 R/S). This mixture was subjected to the next step without any additional purification. MS (ES+): mass calculated for C26H22Cl2N2O3, 480.10; m/z found, 480.8 [M+H]+. 1H NMR (400 MHz, CDCl3): 7.31-7.09 (m, 8H), 6.91-6.86 (m, 3H), 6.21 (s, 1H), 4.12-4.08 (dd, J=5.8, 9.6 Hz, 1H), 3.82 (s, 3H), 3.54-3.49 (dd, J=9.6, 14.9 Hz, 1H), 3.13-3.08 (dd, J=5.8, 14.9 Hz, 1H), 2.35 (s, 3H).