Hydrochloric Acid → 649551-06-4

HRID 1823233Notes

Reaction equation

HRID 1823233 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

HCID 313Hydrochloric AcidHCID 69199557HCID 69199557, compound

Product 1

HCID 11488979649551-06-4Yield 98%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

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).

Workup

  1. customA 500-mL, 1-necked round-bottomed flask equipped with a magnetic stirring bar
  2. customthe heating source was removed
  3. customreaction flask
  4. temperaturecooled to rt
  5. concentrationThe mixture was concentrated under reduced pressure
  6. customto remove most of acetic acid
  7. addition250 mL of EtOAc was added
  8. washThe EtOAc solution was then washed with H2O (50 mL) and brine (50 mL)
  9. dry with materialdried over Na2SO4
  10. customThe solvents were removed under reduced pressure

Sources & evidence

ORD record
ord-34848577636b472cb4a1b80491d30f6d
Source dataset
uspto-grants-2006_05
Patent number
US07037931B2

Reaction notes

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