2-(4-Chloro-benzyl)-3-hydroxy-8-phenyl-quinoline-4-carboxylic Acid → 8-(sec-butyl)-2-(4-chlorobenzyl)-3-hydroxyquinoline-4-carboxylic Acid

HRID 2375520Notes

Reaction equation

HRID 2375520 reaction equation
[Cl:1][C:2]1[CH:28]=[CH:27][C:5]([CH2:6][C:7]2[C:16]([OH:17])=[C:15]([C:18]([OH:20])=[O:19])[C:14]3[C:9](=[C:10]([C:21]4[CH:26]=CC=[CH:23][CH:22]=4)[CH:11]=[CH:12][CH:13]=3)[N:8]=2)=[CH:4][CH:3]=1.C(C1C=CC=C2C=1NC(=O)C2=O)(CC)C.C(OCC(=O)CC1C=CC(Cl)=CC=1)(=O)C>>[CH:21]([C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[C:9]=1[N:8]=[C:7]([CH2:6][C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:28][CH:27]=1)[C:16]([OH:17])=[C:15]2[C:18]([OH:20])=[O:19])([CH2:22][CH3:23])[CH3:26]

Participants

4

Reactant 3

HCID 113837082-(4-Chloro-benzyl)-3-hydroxy-8-phenyl-quinoline-4-carboxylic AcidHCID 122224641-(Acetyloxy)-3-(4-chlorophenyl)-2-propanoneHCID 122727957-Sec-butylisatin

Product 1

HCID 161001488-(sec-butyl)-2-(4-chlorobenzyl)-3-hydroxyquinoline-4-carboxylic Acid

Procedure

This compound was synthesized by the procedure described above for Compound 2, reacting 7-sec-butylisatin (1.00 g, 4.92 mmol) with 3-(4-chlorophenyl)-2-oxopropyl acetate (1.39 g, 6.15 mmol). The crude acid was purified as described above for Compound 3 and, after hydrochloric acid treatment of an acetonitrile/water solution of the triethylammonium salt, extracted into ethyl acetate (3×), washed with brine, dried over anhydrous magnesium sulfate, filtered, evaporated and lyophilized. It was then purified (preparative HPLC, eluting with acetonitrile/water/triethylamine), and converted back to the free acid and extracted and evaporated once more as described above. A final lyophilization step gave product Compound 10 as a fluffy, bright yellow solid (72 mg, 3.9% yield): 1H NMR (400 MHz, DMSO-D6) δ 0.74 (t, J=7.3 Hz, 3H) 1.22 (d, J=6.8 Hz, 3H) 1.61 (m, 2H) 3.91 (m, 1H) 4.32 (dd, 2H) 7.34 (m, 4H) 7.39 (d, J=6.1 Hz, 1H) 7.51 (dd, J=8.6, 7.3 Hz, 1H) 8.25 (dd, J=8.3, 1.3 Hz, 1H); HRMS (ESI/FTMS) calcd for C21H21ClNO3 (MH+) 370.1205, found 370.1204. Anal. Calcd for C21H20ClNO3: C, 68.20; H, 5.45; N, 3.79. Found: C, 67.97; H, 5.47; N, 3.53.

Workup

  1. customThis compound was synthesized by the procedure
  2. customThe crude acid was purified
  3. extractionafter hydrochloric acid treatment of an acetonitrile/water solution of the triethylammonium salt, extracted into ethyl acetate (3×)
  4. washwashed with brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customIt was then purified
  9. wash(preparative HPLC, eluting with acetonitrile/water/triethylamine)
  10. extractionextracted
  11. customevaporated once more

Sources & evidence

ORD record
ord-19277b79135542ff9d94378f02d883e4
Source dataset
uspto-grants-2008_12
Patent number
US07465799B2

Reaction notes

Loading…