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

HRID 2235657Notes

Reaction equation

HRID 2235657 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:37]4[CH:42]=[CH:41][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:39][CH:38]=4)=[CH:34][C:35]=3[CH3:36])=[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:52]([O-])([O-])=[O:53].[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:37]4[CH:38]=[CH:39][C:40]([C:43]([F:46])([F:45])[F:44])=[CH:41][CH:42]=4)=[CH:34][C:35]=3[CH3:36])=[CH:27][CH:28]=2)[CH2:7][C:8]([O:53][CH3:52])=[O:9])=[N:2]1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 59300606(4S)-3-((3S)-3-(3-Isoxazolyl)-3-(4-(((3-methyl-5-(4-(trifluoromethyl)phenyl)-2-thienyl)methyl)oxy)phenyl)propanoyl)-4-(phenylmethyl)-1,3-oxazolidin-2-one

Product 1

HCID 59300676Methyl (3S)-3-(3-isoxazolyl)-3-(4-(((3-methyl-5-(4-(trifluoromethyl)phenyl)-2-thienyl)methyl)oxy)phenyl)propanoateYield 88%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 62.8 (94 mg, 0.15 mmol) in THF (1.5 mL) were added 30% H2O2 (0.17 mL, 1.50 mmol) and 1N LiOH (0.73 mL, 0.73 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 organics were washed with 1N Na2SO3 (pH 3) and brine, dried (Na2SO4), and concentrated. The residue was dissolved in 9:1 MeCN/DMF (1.5 mL), and to the solution were added K2CO3 (30 mg, 0.22 mmol) and iodomethane (20 μL, 0.22 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 62.9 (64 mg, 88%) as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.28 (d, 1H), 7.65 (d, 2H), 7.60 (d, 2H), 7.20 (d, 2H), 7.15 (s, 1H), 6.95 (d, 2H), 6.08 (d, 1H), 5.10 (s, 2H), 4.59 (t, 1H), 3.64 (s, 3H), 3.31 (dd, 1H), 2.95 (dd, 1H), 2.28 (s, 3H).

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. dissolutionThe residue was dissolved in 9:1 MeCN/DMF (1.5 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-fa9f1b8575db4dd890ebf9c9329c3c64
Source dataset
uspto-grants-2010_05
Patent number
US07714008B2

Reaction notes

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