Hydrochloric Acid → 6-(4-{[3-(2,6-Dichlorophenyl)-5-(1-Methylethyl)isoxazol-4-Yl]methoxy}phenyl)quinoline-2-Carboxylic Acid

HRID 2423389Notes

Reaction equation

HRID 2423389 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:13]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]=[C:27]([C:32]([O:34]C)=[O:33])[CH:26]=[CH:25]4)=[CH:18][CH:17]=2)=[C:12]([CH:36]([CH3:38])[CH3:37])[O:11][N:10]=1.[OH-].[Na+].CO.Cl>O.C1COCC1>[Cl:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[C:3]=1[C:9]1[C:13]([CH2:14][O:15][C:16]2[CH:21]=[CH:20][C:19]([C:22]3[CH:23]=[C:24]4[C:29](=[CH:30][CH:31]=3)[N:28]=[C:27]([C:32]([OH:34])=[O:33])[CH:26]=[CH:25]4)=[CH:18][CH:17]=2)=[C:12]([CH:36]([CH3:38])[CH3:37])[O:11][N:10]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 14798Sodium HydroxideHCID 59321513Methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate

Product 1

HCID 247719836-(4-{[3-(2,6-Dichlorophenyl)-5-(1-Methylethyl)isoxazol-4-Yl]methoxy}phenyl)quinoline-2-Carboxylic AcidYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A stirred mixture of methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylate (245 g, 0.45 mol), NaOH (36 g, 0.90 mol) dissolved in water (225 mL), methanol (0.5 L) and THF (1.2 L) was heated at 65° C. for 90 min. The mixture was cooled to room temperature, treated with 6 N HCl (150 mL) and stirred at room temperature for 30 min. The resulting precipitate was collected by filtering, washed with water (2×1 L) and dried overnight at 45° C. in a vacuum oven to yield 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-2-quinolinecarboxylic acid (162 g, 68%). A second crop of material was similarly obtained (27.2 g, 11%). 1H NMR (400 MHz, DMSO-d6): 8.48 (d, J=9 Hz, 1H), 8.24 (d, J=2 Hz, 1H), 8.17 (d, J=9 Hz, 1H), 8.09 (d, J=9 Hz, 2H), 7.72 (d, J=9 Hz, 2H), 7.62 (d, J=8 Hz, 2H), 7.53 (m, 1H), 6.92 (d, J=9 Hz, 2H), 4.88 (s, 2H), 3.46 (m, 1H), 1.32 (d, J=7 Hz, 6H). ES-LCMS m/z 533 (M+H)+.

Workup

  1. customThe resulting precipitate was collected
  2. filtrationby filtering
  3. washwashed with water (2×1 L)
  4. customdried overnight at 45° C. in a vacuum oven

Sources & evidence

ORD record
ord-c3366ffc1da249de8982d2e3d63f8893
Source dataset
uspto-grants-2011_06
Patent number
US07960552B2

Reaction notes

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