Hydrogen Peroxide → HCID 58566409, compound

HRID 445891Notes

Reaction equation

HRID 445891 reaction equation
[OH-].[Li+].OO.C([C@H]1N([C:17](=[O:41])[C@H:18]([CH3:40])[CH2:19][C:20]2[CH:25]=[CH:24][C:23]([O:26][CH2:27][C:28]3[C:36]4[O:35][C:34]([CH3:38])([CH3:37])[CH2:33][C:32]=4[CH:31]=[C:30]([F:39])[CH:29]=3)=[CH:22][CH:21]=2)C(=O)CC1)C1C=CC=CC=1.S([O-])([O-])=[O:44].[Na+].[Na+]>O.O1CCCC1.O>[F:39][C:30]1[CH:29]=[C:28]([CH2:27][O:26][C:23]2[CH:22]=[CH:21][C:20]([CH2:19][C@@H:18]([CH3:40])[C:17]([OH:41])=[O:44])=[CH:25][CH:24]=2)[C:36]2[O:35][C:34]([CH3:37])([CH3:38])[CH2:33][C:32]=2[CH:31]=1

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 24437Sodium SulfiteHCID 58566675HCID 58566675, compound

Product 1

HCID 58566409HCID 58566409, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
0 °C

Procedure

To a solution of lithium hydroxide (65 mg, 1.55 mmol) in water (2 mL) was added 30% hydrogen peroxide (0.4 mL, 3.88 mmol) and stirred for 30 minutes. The solution was cooled to 0° C. and was added to a solution of (S)-5-benzyl-1-((R)-3-(4-((5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoyl)pyrrolidin-2-one (805) (500 mg, 0.97 mmol) in 4:1 tetrahydrofuran/water (5 mL) at 0° C. The reaction was stirred for 1 hour at 0° C. and was quenched with sodium sulfite (489 mg, 3.88 mmol) in water (3 mL). The solvent was removed in vacuo at room temperature. The solution was cooled to 0° C. and was acidified with 6N HCl. The aqueous layer was extracted with ethyl aceate, dried over sodium sulfate, filtered, and concentrated in vacuo. The crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%) to afford (R)-3-(4-((5-fluoro-2,2-dimethyl-2,3-dihydrobenzofuran-7-yl)methoxy)phenyl)-2-methylpropanoic acid (94). 1H NMR (400 MHz, CDCl3) δ: 7.09 (d, J=8.5 Hz, 2H), 6.97 (d, J=9.7 Hz, 1H), 6.91 (d, J=8.5 Hz, 2H), 6.79 (d, J=7.6 Hz, 1H), 4.97 (s, 2H), 3.05-2.95 (m, 3H), 2.75-2.58 (m, 2H), 1.48 (s, 6H), 1.16 (d, J=4.0 Hz, 3H). LC-MS ESI m/z: found 357.0 [M−H]−.

Workup

  1. stirringThe reaction was stirred for 1 hour at 0° C.
  2. customThe solvent was removed in vacuo at room temperature
  3. temperatureThe solution was cooled to 0° C.
  4. extractionThe aqueous layer was extracted with ethyl aceate
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude compound was purified by flash column chromatography on silica gel with hexanes and EtOAc (20%)

Sources & evidence

ORD record
ord-05f25cf3c24d43f293dbf00fc45d555c
Source dataset
uspto-grants-2013_07
Patent number
US08476308B2

Reaction notes

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