Lithium hydroxide, monohydrate → 3-(1-{[3-Methoxy-4-(3-[2-methylphenyl]-ureido)-phenyl]-acetyl}-1,2,3,4-tetrahydro-quinolin-6-yl)-propionic Acid

HRID 396708Notes

Reaction equation

HRID 396708 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:23]2[C:32]3[C:27](=[CH:28][C:29]([CH2:33][CH2:34][C:35]([O:37]CC)=[O:36])=[CH:30][CH:31]=3)[CH2:26][CH2:25][CH2:24]2)=[O:22])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[C:14]([CH3:19])=[CH:15][CH:16]=[CH:17][CH:18]=1)=[O:11].O.[OH-].[Li+]>C(O)C.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH2:20][C:21]([N:23]2[C:32]3[C:27](=[CH:28][C:29]([CH2:33][CH2:34][C:35]([OH:37])=[O:36])=[CH:30][CH:31]=3)[CH2:26][CH2:25][CH2:24]2)=[O:22])[CH:6]=[CH:7][C:8]=1[NH:9][C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[CH3:19])=[O:11]

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 23003938Ethyl 3-[1-(2-{3-Methoxy-4-[(2-toluidinocarbonyl)amino]phenyl}acetyl)-1,2,3,4-tetrahydro-6-quinolinyl]propanoate

Product 1

HCID 99139473-(1-{[3-Methoxy-4-(3-[2-methylphenyl]-ureido)-phenyl]-acetyl}-1,2,3,4-tetrahydro-quinolin-6-yl)-propionic AcidYield 65.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
20 °C

Procedure

A solution of ethyl 3-(1-{[3-methoxy-4-[(2-toluidinocarbonyl)amino]phenyl}acetyl)-1,2,3,4-tetrahydroquinolin-6-yl)-propanoate (0.24 g, Reference Example 1) in anhydrous ethanol (4 ml), at 20° C., was treated dropwise with a solution of lithium hydroxide monohydrate (33 mg) in distilled water (1 ml). After stirring for 3 hours at 20° C. the reaction mixture was evaporated under reduced pressure (2.7 kPa) at 40° C. The residue was treated with distilled water (35 ml) and the resulting solution was washed twice with diethyl ether (20 ml), then acidified to pH 3 by addition of hydrochloric acid (0.8 ml, 1N) and then extracted twice with ethyl acetate (25 ml). The combined organic extracts were washed twice with water (5 ml), then dried over magnesium sulfate and then evaporated under reduced pressure (2.7 kPa) at 40° C. The resulting white foamy solid (191 mg) was subjected to chromatography on silica gel plates (4 plates, 20×20 cm, thickness=0.5 mm), eluting with a mixture of dichloromethane and methanol (9:1, v/v) to give the title compound (148 mg) as a white foamy solid. 1H NMR (300 MHz, (CD3)2SO): δ 1.81 (m, 2H); 2.27 (s, 3H); from 2.45-2.70 (m, 4H), 2.82 (t, J=7.5 Hz, 2H); 3.72 (t, J=6.5 Hz, 2H); 3.82 (s, 2H); 3.87 (s, 3H); 6.60-7.50 (m, 8H); 7.82 (d, J=8 Hz, 1H); 8.05 (d, J=8 Hz, 1H); 8.50 (s, 1H); 8.60 (s, 1H). MS (Electron Impact recorded on a Finnigan SSQ 7000 spectrometer at 70 eV) 501 (M+).

Workup

  1. customwas evaporated under reduced pressure (2.7 kPa) at 40° C
  2. additionThe residue was treated with distilled water (35 ml)
  3. washthe resulting solution was washed twice with diethyl ether (20 ml)
  4. additionacidified to pH 3 by addition of hydrochloric acid (0.8 ml, 1N)
  5. extractionextracted twice with ethyl acetate (25 ml)
  6. washThe combined organic extracts were washed twice with water (5 ml)
  7. dry with materialdried over magnesium sulfate
  8. customevaporated under reduced pressure (2.7 kPa) at 40° C
  9. washthickness=0.5 mm), eluting with a mixture of dichloromethane and methanol (9:1

Sources & evidence

ORD record
ord-2560ac1391874802a28521c6a0338f03
Source dataset
uspto-grants-2003_08
Patent number
US06608084B1

Reaction notes

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