Hydrogen Peroxide → (R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoic acid

HRID 660369Notes

Reaction equation

HRID 660369 reaction equation
C([C@@H]1COC(=O)N1[C:14](=[O:34])[C@H:15]([CH2:19][C:20]1[CH:28]=[C:27]2[C:23]([CH:24]=[N:25][N:26]2[CH2:29][CH2:30][CH2:31][O:32][CH3:33])=[CH:22][CH:21]=1)[CH:16]([CH3:18])[CH3:17])C1C=CC=CC=1.OO.[Li+].[OH-].[O-:39]S([O-])=O.[Na+].[Na+]>C1COCC1.O>[CH3:33][O:32][CH2:31][CH2:30][CH2:29][N:26]1[C:27]2[C:23](=[CH:22][CH:21]=[C:20]([CH2:19][C@H:15]([CH:16]([CH3:17])[CH3:18])[C:14]([OH:34])=[O:39])[CH:28]=2)[CH:24]=[N:25]1

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 24437Sodium SulfiteHCID 68786317(R)-4-benzyl-3-((R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoyl)-oxazolidin-2-one

Product 1

HCID 68783318(R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoic acidYield 81%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of (R)-4-benzyl-3-((R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoyl)oxazolidin-2-one (230 mg, 0.5 mmol) in 3:1 THF/H2O (8 mL) cooled in an ice-water bath, were added 30% aq H2O2 (0.5 mL, 3.5 mmol) and LiOH (60 mg, 1.1 mmol). The mixture was stirred at rt for 12 h. The mixture was cooled to 0° C. and 10% aq Na2SO3 (5 mL) was added dropwise. The solvent was removed in vacuo and the aqueous phase was washed with Et2O. The pH of the aqueous layer was adjusted to 3 by addition of 1 N aq HCl. The mixture was extracted with CH2Cl2 (3×10 mL). The combined organic layers were washed with brine, dried over Na2SO4, and evaporated to give (R)-2-((1-(3-methoxypropyl)-1H-indazol-6-yl)methyl)-3-methylbutanoic acid (123 mg, 81%). 1H NMR (400 MHz, CDCl3): 1.07 (m, 6H), 1.99 (m, 1H), 2.56 (m, 1H), 3.00 (m, 2H), 3.24 (m, 2H), 2.99 (s, 3H), 4.10 (m, 1H), 4.40 (m, 2H), 6.98 (m, 1H), 7.23 (m, 1H), 7.59 (m, 1H), 7.92 (m, 1H). MS: 305 (M++1)

Workup

  1. temperatureThe mixture was cooled to 0° C.
  2. customThe solvent was removed in vacuo
  3. washthe aqueous phase was washed with Et2O
  4. additionThe pH of the aqueous layer was adjusted to 3 by addition of 1 N aq HCl
  5. extractionThe mixture was extracted with CH2Cl2 (3×10 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated

Sources & evidence

ORD record
ord-261ffc26162b4b7cb475cf9eb8bd301c
Source dataset
uspto-grants-2011_12
Patent number
US08084485B2

Reaction notes

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