Methanol → Gsk-8062

HRID 1693645Notes

Reaction equation

HRID 1693645 reaction equation
CO.[OH-].[Na+].[Cl:5][C:6]1[CH:11]=[CH:10][CH:9]=[C:8]([Cl:12])[C:7]=1[C:13]1[C:17]([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[C:32]([C:36]([O:38]C)=[O:37])=[CH:31][CH:30]=[CH:29]4)=[CH:22][CH:21]=2)=[C:16]([CH:40]([CH3:42])[CH3:41])[O:15][N:14]=1>O1CCCC1>[Cl:12][C:8]1[CH:9]=[CH:10][CH:11]=[C:6]([Cl:5])[C:7]=1[C:13]1[C:17]([CH2:18][O:19][C:20]2[CH:25]=[CH:24][C:23]([C:26]3[CH:27]=[C:28]4[C:33](=[CH:34][CH:35]=3)[C:32]([C:36]([OH:38])=[O:37])=[CH:31][CH:30]=[CH:29]4)=[CH:22][CH:21]=2)=[C:16]([CH:40]([CH3:42])[CH3:41])[O:15][N:14]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 59264878Methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylate

Product 1

HCID 16214849Gsk-8062Yield 91.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methanol (380 mL) and 5 N sodium hydroxide solution (190 mL) were added to a stirred solution of methyl 6-[4-({[3-(2,6-dichlorophenyl)-5-(1-methylethyl)-4-isoxazolyl]methyl}oxy)phenyl]-1-naphthalenecarboxylate (190 g, 0.35 mol) in tetrahydrofuran (1 L). The resulting solution was heated to reflux for 1.5 h. The mixture was cooled to room temperature and concentrated to remove methanol and tetrahydrofuran. The residue was diluted with water (500 mL), acidified with 6 N HCl and the supernatant was decanted from the taffy-like solid. The solid was crystallized from ethyl acetate (1 L) to give 170 g of the product as off-white crystals. 1H NMR (DMSO-d6): 9.02 (d, J=9 Hz, 1H), 8.01 (s, 1H), 7.80 (d, J=8 Hz, 1H), 7.73 (d, J=7 Hz, 1H), 7.68-7.61 (m, 5H), 7.53 (dd, J=7, 9 Hz, 1H), 7.38 (t, J=8, 15 Hz, 1H), 6.88 (d, J=9 Hz, 2H), 4.85 (s, 2H), 3.46 (septet, J=7 Hz, 1H), 1.32 (d, J=7 Hz, 6H). ESI-LCMS m/z 532 (M+H)+.

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 1.5 h
  3. concentrationconcentrated
  4. customto remove methanol and tetrahydrofuran
  5. additionThe residue was diluted with water (500 mL)
  6. customthe supernatant was decanted from the taffy-like solid
  7. customThe solid was crystallized from ethyl acetate (1 L)

Sources & evidence

ORD record
ord-adea229216aa4894a5d2bac8cb2c5c13
Source dataset
uspto-grants-2012_04
Patent number
US08158665B2

Reaction notes

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