Sodium Hydroxide → LY-465608

HRID 398103Notes

Reaction equation

HRID 398103 reaction equation
C([O:3][C:4](=[O:36])[C:5]([CH3:35])([O:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:28]=[CH:27][C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:25][CH:24]=3)[O:20][C:21]=2[CH3:22])=[CH:10][CH:9]=1)[CH3:6])C.[OH-].[Na+]>CO>[CH3:35][C:5]([O:7][C:8]1[CH:9]=[CH:10][C:11]([O:14][CH2:15][CH2:16][C:17]2[N:18]=[C:19]([C:23]3[CH:24]=[CH:25][C:26]([C:29]4[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=4)=[CH:27][CH:28]=3)[O:20][C:21]=2[CH3:22])=[CH:12][CH:13]=1)([CH3:6])[C:4]([OH:36])=[O:3]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 112370922-Methyl-2-{4-[2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethoxy]phenoxy}propionic acid ethyl ester

Product 1

HCID 9890319LY-465608Yield 67%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

2-Methyl-2-{4-[2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethoxy]phenoxy}propionic acid ethyl ester (12.0 g, 24.7 mmol) was dissolved in methanol (200 mL) and 2N NaOH (150 mL) was added. The resulting cloudy solution became clear after 30 min and the reaction was stirred vigorously overnight. The solution was concentrated under reduced pressure, diluted with H2O (100 mL) and acidified to pH=1 with 5N HCl. The mixture was extracted with ethyl acetate (2×200 mL), dried (MgSO4), and concentrated under reduced pressure to provide an oil. The oil (8.23 g) was recrystallized from ethyl acetate (24 mL) and hexanes (56 mL) to afford 2-methyl-2-{4-[2-(5-methyl-2-biphenyl-4-yl-oxazol-4-yl)ethoxy]phenoxy}propionic acid (7.57 g, 67%) as colorless needles after drying at 50° C. under vacuum for 6 h: Rf=0.14 in 35% ethyl acetate/hexanes; mp 123-124° C.; 1H NMR (400 MHz, CDCl3) δ8.05 (d, J=8.0 Hz, 2H), 7.67 (d, J=8.0 Hz, 2H), 7.66-7.63 (m, 2H), 7.46 (t, J=7.6 Hz, 2H), 7.38 (t, J=7.6 Hz, 11H), 6.91-6.79 (m, 4H), 4.21 (t, J=6.4 Hz, 2H), 3.01 (t, J=6.4 Hz, 2H), 2.40 (s, 3H), 1.53 (s, 6H); MS m/e calculated. for C28H28NO5 (M++1) 458.2, found 458.2.

Workup

  1. concentrationThe solution was concentrated under reduced pressure
  2. additiondiluted with H2O (100 mL)
  3. extractionThe mixture was extracted with ethyl acetate (2×200 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customto provide an oil
  7. customThe oil (8.23 g) was recrystallized from ethyl acetate (24 mL) and hexanes (56 mL)

Sources & evidence

ORD record
ord-64c0e4ed69954d5982b70fc48f69d2f1
Source dataset
uspto-grants-2003_08
Patent number
US06610696B2

Reaction notes

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