Hydrochloric Acid → Methyl (3S)-3-(3-isoxazolyl)-3-(4-(((5-(4-(trifluoromethyl)phenyl)-2-thienyl)methyl)oxy)phenyl)propanoate

HRID 2235649Notes

Reaction equation

HRID 2235649 reaction equation
[O:1]1[CH:5]=[CH:4][C:3]([C@H:6]([C:23]2[CH:28]=[CH:27][C:26]([O:29][CH2:30][C:31]3[S:32][C:33]([C:36]4[CH:41]=[CH:40][C:39]([C:42]([F:45])([F:44])[F:43])=[CH:38][CH:37]=4)=[CH:34][CH:35]=3)=[CH:25][CH:24]=2)[CH2:7][C:8](N2[C@@H](CC3C=CC=CC=3)COC2=O)=[O:9])=[N:2]1.OO.[Li+].[OH-].Cl.[C:51]([O-])([O-])=[O:52].[K+].[K+].IC>C1COCC1.CCOC(C)=O>[O:1]1[CH:5]=[CH:4][C:3]([C@H:6]([C:23]2[CH:24]=[CH:25][C:26]([O:29][CH2:30][C:31]3[S:32][C:33]([C:36]4[CH:37]=[CH:38][C:39]([C:42]([F:45])([F:43])[F:44])=[CH:40][CH:41]=4)=[CH:34][CH:35]=3)=[CH:27][CH:28]=2)[CH2:7][C:8]([O:52][CH3:51])=[O:9])=[N:2]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 59300625(4S)-3-((3S)-3-(3-isoxazolyl)-3-(4-(((5-(4-(trifluoromethyl)phenyl)-2-thienyl)methyl)oxy)phenyl)propanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one

Product 1

HCID 59300661Methyl (3S)-3-(3-isoxazolyl)-3-(4-(((5-(4-(trifluoromethyl)phenyl)-2-thienyl)methyl)oxy)phenyl)propanoate

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 61.5 (76 mg, 0.12 mmol) in THF (1 mL) were added 30% H2O2 (0.14 mL, 1.2 mmol) and 1N LiOH (0.60 mL, 0.60 mmol) at 0° C. The mixture was stirred for 1 hour at 0° C., adjusted to pH 3 with aqueous HCl, and extracted with EtOAc. The combined organic layers were washed with 1N Na2SO3 (pH 3) and brine, dried (Na2SO4), and concentrated. The residue was dissolved in 9:1 MeCN/DMF (1 mL), and to the solution were added K2CO3 (25 mg, 0.18 mmol) and iodomethane (11 μL, 0.18 mmol). The mixture was stirred overnight at room temperature, diluted with EtOAc, washed with water and brine, dried (Na2SO4), and concentrated. The crude product was chromatographed on silica gel (0-40% EtOAc/hexane) to afford 61.6 as a white solid.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layers were washed with 1N Na2SO3 (pH 3) and brine
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in 9:1 MeCN/DMF (1 mL)
  6. stirringThe mixture was stirred overnight at room temperature
  7. washwashed with water and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customThe crude product was chromatographed on silica gel (0-40% EtOAc/hexane)

Sources & evidence

ORD record
ord-ddf8712f666b49b78ab2fedab7ea0991
Source dataset
uspto-grants-2010_05
Patent number
US07714008B2

Reaction notes

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