Hydrochloric Acid → (3S)-3-(4-(((5-(4-butylphenyl)-2-thienyl)methyl)oxy)phenyl)-3-(3-isoxazolyl)propanoic acid

HRID 1675305Notes

Reaction equation

HRID 1675305 reaction equation
[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:15][C:14]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][C:21]([C@@H:24]([C:41]4[CH:45]=[CH:44][O:43][N:42]=4)[CH2:25][C:26](N4[C@@H](CC5C=CC=CC=5)COC4=O)=[O:27])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4].[OH:46]O.[Li+].[OH-].Cl>C1COCC1>[CH2:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:15][C:14]([CH2:16][O:17][C:18]3[CH:23]=[CH:22][C:21]([C@@H:24]([C:41]4[CH:45]=[CH:44][O:43][N:42]=4)[CH2:25][C:26]([OH:27])=[O:46])=[CH:20][CH:19]=3)=[CH:13][CH:12]=2)=[CH:7][CH:6]=1)[CH2:2][CH2:3][CH3:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 59300558(4S)-3-((3S)-3-(4-(((5-(4-butylphenyl)-2-thienyl)methyl)oxy)phenyl)-3-(3-isoxazolyl)propanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one

Product 1

HCID 59300564(3S)-3-(4-(((5-(4-butylphenyl)-2-thienyl)methyl)oxy)phenyl)-3-(3-isoxazolyl)propanoic acidYield 8.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 60.6 (26 mg, 0.042 mmol) in THF (0.4 mL) were added 30% H2O2 (47 μL, 0.42 mmol) and 1N LiOH (0.21 mL, 0.21 mmol) at 0° C. The mixture was stirred for 1 h at 0° C., adjusted to pH 3 with aqueous HCl, and extracted with EtOAc. The combined organics were washed with 1N Na2SO3 (pH 3) and brine, dried (Na2SO4), and concentrated. The crude product was chromatographed on silica gel (10-45% EtOAc/hexane) and further purified by preparative thin layer chromatography (50% EtOAc/hexane) to afford 60 (1.6 mg, 8%) as a white solid. 1H NMR (400 MHz, CDCl3) δ 8.28 (d, 1H), 7.48 (d, 2H), 7.18 (m, 4H), 7.14 (d, 1H), 7.04 (d, 1H), 6.94 (d, 2H), 6.07 (d, 1H), 5.17 (s, 2H), 4.55 (t, 1H), 3.35 (dd, 1H), 2.98 (dd, 1H), 2.61 (t, 2H), 1.60 (m, 2H), 1.37 (m, 2H), 0.93 (t, 2H).

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organics were washed with 1N Na2SO3 (pH 3) and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customThe crude product was chromatographed on silica gel (10-45% EtOAc/hexane)
  6. customfurther purified by preparative thin layer chromatography (50% EtOAc/hexane)

Sources & evidence

ORD record
ord-f9b057fe745c42bd9e618d219e8f39e5
Source dataset
uspto-grants-2011_08
Patent number
US08003648B2

Reaction notes

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