2-Methoxyphenylacetic acid → HCID 57214342, compound

HRID 1420850Notes

Reaction equation

HRID 1420850 reaction equation
S(Cl)(Cl)=O.[CH3:5][O:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH2:13][C:14]([OH:16])=O.[CH2:17]([C@H:24]1[CH2:28][O:27][C:26](=[O:29])[NH:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.C([Li])CCC.[Cl-].[NH4+]>C1(C)C=CC=CC=1.O1CCCC1.CN(C)C=O>[CH2:17]([C@H:24]1[CH2:28][O:27][C:26](=[O:29])[N:25]1[C:14](=[O:16])[CH2:13][C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=1[O:6][CH3:5])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1

Participants

9

Reactant 5

HCID 71342-Methoxyphenylacetic acidHCID 24386Thionyl ChlorideHCID 25517Ammonium ChlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 178418339Butyllithium

Product 1

HCID 57214342HCID 57214342, compoundYield 47.4%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
50 °C

Procedure

Thionyl chloride (6.91 mL) was added slowly to a warmed (50° C.) solution of 2-methoxyphenylacetic acid (13.77 g, 0.083 mol) and dimethylformamide (0.1 mL) in toluene (50 mL) and the mixture was stirred at 50° C. for 2 h. The solvent was evaporated under reduced pressure and the residue was dissolved in tetrahydrofuran (50 mL). To a cooled solution (-20° C.) of (4S)-4-benzyl oxazolidine-2-one (14.7 g, 83 mmol) in tetrahydrofuran (80 mL) was slowly added n-butyl lithium (1.6 M, 52 mL, 83 mmol) and the mixture was warmed to 0° C. To this solution was slowly added the solution of the acid chloride (above) in tetrahydrofuran over 20 min. The mixture was warmed to room temperature and was stirred for 72 h. Saturated aqueous ammonium chloride was added and the mixture was extracted with ethyl acetate. The combined organic fractions was washed with water and brine, dried (MgSO4) and the solvent was evaporated under reduced pressure. The residue was purified by chromatography on silica gel eluting with hexane/EtOAc (90:10 increasing to 50:50) to give the title compound (12.8 g) 1H NMR (360 MHz, CDCl3) δ7.37-7.15 (7 H, m), 6.92 (2 H, m), 4.71 (1 H, m), 4.30 (1 H, d, J 17.6 Hz), 4.26-4.17 (4 H, m), 3.82 (3 H, s), 3.29 (1 H, dd, J 13.4, 3.1 Hz), and 2.81 (1 H, dd, J 13.3 9.4 Hz).

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionthe residue was dissolved in tetrahydrofuran (50 mL)
  3. temperaturethe mixture was warmed to 0° C
  4. temperatureThe mixture was warmed to room temperature
  5. stirringwas stirred for 72 h
  6. extractionthe mixture was extracted with ethyl acetate
  7. washThe combined organic fractions was washed with water and brine
  8. dry with materialdried (MgSO4)
  9. customthe solvent was evaporated under reduced pressure
  10. customThe residue was purified by chromatography on silica gel eluting with hexane/EtOAc (90:10 increasing to 50:50)

Sources & evidence

ORD record
ord-2197ceedc42e488d860a552fc57a59ff
Source dataset
uspto-grants-2000_06
Patent number
US06071927

Reaction notes

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