Hydrochloric Acid → 6-[4-({[5-Cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid

HRID 2423411Notes

Reaction equation

HRID 2423411 reaction equation
[CH:1]1([C:6]2[O:10][N:9]=[C:8]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[C:7]=2[CH2:19][O:20][C:21]2[CH:26]=[CH:25][C:24]([C:27]3[CH:28]=[C:29]4[C:34](=[CH:35][CH:36]=3)[N:33]=[C:32]([C:37]([O:39]C)=[O:38])[CH:31]=[CH:30]4)=[CH:23][CH:22]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.O1CCCC1.[OH-].[Na+].Cl>C(OCC)(=O)C.O.CO>[CH:1]1([C:6]2[O:10][N:9]=[C:8]([C:11]3[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][C:12]=3[Cl:18])[C:7]=2[CH2:19][O:20][C:21]2[CH:22]=[CH:23][C:24]([C:27]3[CH:28]=[C:29]4[C:34](=[CH:35][CH:36]=3)[N:33]=[C:32]([C:37]([OH:39])=[O:38])[CH:31]=[CH:30]4)=[CH:25][CH:26]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 59321578Methyl 6-[4-({[5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

Product 1

HCID 593214686-[4-({[5-Cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acidYield 82%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 6-[4-({[5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (73 mg, 0.13 mmol) in 2:1 tetrahydrofuran:methanol (1.5 mL) was added 1N sodium hydroxide (0.19 mL, 0.19 mmol). A solid was seen to precipitate. The mixture was heated in a microwave reactor at 120° C. for 500 seconds and then was concentrated and the residue was taken up with water and hydrochloric acid (0.19 mL, 0.19 mmol) was added. Ethyl acetate was added and the layers were separated. The aqueous layer was extracted once more with ethyl acetate. The combined organic layers were washed with brine and concentrated to afford 6-[4-({[5-cyclopentyl-3-(2,6-dichlorophenyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid (58 mg, 82%). 1H-NMR (400 MHz, DMSO-d6) δ 13.36 (br s, 1H), 8.53 (d, J=9 Hz, 1H), 8.27 (s, 1H), 8.18-8.08 (m, 3H), 7.73 (d, J=9 Hz, 2H), 7.63-7.51 (m, 3H), 6.92 (d, J=9 Hz, 2H), 4.87 (s, 2H), 3.59-3.51 (m, 1H), 2.11-2.03 (m, 2H), 1.84-1.64 (m, 6H). HRMS (ESI) C31H24Cl2N2O4 calculated: 559.1186 (M+H)+, found: 559.1183 (M+H)+.

Workup

  1. customto precipitate
  2. concentrationwas concentrated
  3. additionwas added
  4. customthe layers were separated
  5. extractionThe aqueous layer was extracted once more with ethyl acetate
  6. washThe combined organic layers were washed with brine
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-fd25e6a64bff43eea05ee3f89fa5cf9e
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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