Methanol → Gsk-8062

HRID 646002Notes

Reaction equation

HRID 646002 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): δ 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, H), 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-7d0643d45f414a6dbb3d52dc8668d36c
Source dataset
uspto-grants-2010_04
Patent number
US07705028B2

Reaction notes

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