Hydrochloric Acid → (S)-3-(5'-fluoro-2,2-dimethyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)-5-(2-oxooxazolidin-3-yl)benzoic acid

HRID 1805362Notes

Reaction equation

HRID 1805362 reaction equation
C[O:2][C:3](=[O:31])[C:4]1[CH:9]=[C:8]([N:10]2[CH2:14][CH2:13][O:12][C:11]2=[O:15])[CH:7]=[C:6]([N:16]2[C:24]3[C:19](=[CH:20][C:21]([F:25])=[CH:22][CH:23]=3)[C@@:18]3([CH2:27][C:26]3([CH3:29])[CH3:28])[C:17]2=[O:30])[CH:5]=1.Cl>O1CCCC1.[OH-].[Na+].O.C(OCC)(=O)C>[F:25][C:21]1[CH:20]=[C:19]2[C:24](=[CH:23][CH:22]=1)[N:16]([C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([N:10]3[CH2:14][CH2:13][O:12][C:11]3=[O:15])[CH:7]=1)[C:3]([OH:31])=[O:2])[C:17](=[O:30])[C@@:18]12[CH2:27][C:26]1([CH3:29])[CH3:28]

Participants

7

Reactant 2

HCID 313Hydrochloric AcidHCID 58305358(S)-methyl-3-(5'-fluoro-2,2-dimethyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)-5-(2-oxooxazolidin-3-yl)benzoate

Product 1

HCID 58305295(S)-3-(5'-fluoro-2,2-dimethyl-2'-oxospiro[cyclopropane-1,3'-indoline]-1'-yl)-5-(2-oxooxazolidin-3-yl)benzoic acidYield 50%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 14798Sodium HydroxideSolvent

Conditions

Temperature
25 °C

Procedure

A mixture of (R) and (S)-methyl-3-(5′-fluoro-2,2-dimethyl-2′-oxospiro[cyclopropane-1,3′-indoline]-1′-yl)-5-(2-oxooxazolidin-3-yl)benzoate (850 mg, 2.4 mmol) in tetrahydrofuran (10 mL) and 30% sodium hydroxide in water (5 mL) was stirred at 25° C. for 16 hours. The mixture was neutralized with a 2N aqueous hydrochloric acid solution, diluted with ethyl acetate (50 mL), washed with water, dried over anhydrous sodium sulfate and then concentrated in vacuo. Purification by waters automated flash system (column: Xterra 30 mm×100 mm, sample manager 2767, pump 2525, detector: ZQ mass and UV 2487, solvent system: acetonitrile and 0.1% trifluoro-acetic acid in water) afforded the title compound (410 mg, 50%) as a white solid: LC/MS m/e calcd. for C20H18FNO3: 340, observed (M+H)+: 340.; 1H NMR (400 MHz, MeOD) δppm 1.50 (s, 3 H) 1.57 (s, 3 H) 1.86 (d, J=4.29 Hz, 1 H) 1.93 (d, J=4.55 Hz, 1 H) 4.22 (t, J=7.96 Hz, 2 H) 4.56 (t, J=7.96 Hz, 2 H) 6.86-6.94 (m, 1 H) 6.94-7.02 (m, 1 H) 7.06 (d, J=8.59 Hz, 1 H) 7.84 (s, 1 H) 8.03 (br. s., 1 H) 8.25 (br. s., 1 H).

Workup

  1. washwashed with water
  2. dry with materialdried over anhydrous sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification by waters

Sources & evidence

ORD record
ord-9c0906537edc403eaf5c1cdf26f33777
Source dataset
uspto-grants-2013_01
Patent number
US08354443B2

Reaction notes

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