Hydrogen Peroxide → (R)-3-hydroxy-3-(3-hydroxymethyl-2-methoxy-pyridin-4-yl)-pentanoic acid

HRID 646622Notes

Reaction equation

HRID 646622 reaction equation
C([SiH2][O:6][C:7](C)(C)[C:8]1[C:9]([O:33][CH3:34])=[N:10][CH:11]=[CH:12][C:13]=1[C:14]([OH:32])([CH2:30][CH3:31])[CH2:15][C:16](N1[C@H](C2C=CC=CC=2)COC1=O)=[O:17])(C)(C)C.[Li+].[OH-:38].OO.[OH-].[Na+]>C1COCC1>[OH:32][C@:14]([C:13]1[CH:12]=[CH:11][N:10]=[C:9]([O:33][CH3:34])[C:8]=1[CH2:7][OH:6])([CH2:30][CH3:31])[CH2:15][C:16]([OH:17])=[O:38]

Participants

6

Reactant 4

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 14798Sodium HydroxideHCID 137328461(R)-3-{3-[3-(tert-butyl-dimethyl-silanyloxymethyl)-2-methoxy-pyridin-4-yl]-3-hydroxy-pentanoyl}-4-phenyl-oxazolidin-2-one

Product 1

HCID 10753497(R)-3-hydroxy-3-(3-hydroxymethyl-2-methoxy-pyridin-4-yl)-pentanoic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3.11 g (R)-3-{3-[3-(tert-butyl-dimethyl-silanyloxymethyl)-2-methoxy-pyridin-4-yl]-3-hydroxy-pentanoyl}-4-phenyl-oxazolidin-2-one (6.04 mmol), as obtainable from example 18, in 35 mL THF were added at 0° C. 37.8 mL aqueous LiOH solution (0.8 M, 30.2 mmol, 5.0 eq) and 3.02 mL aqueous H2O2 solution (10.0 M, 30.2 mmol, 5.0 eq). After 30 min, 220 mL aqueous NaOH solution (2 M) were added and the ice bath was removed. The reaction was monitored by HPLC. After 2 h (<0.2% area (R)-3-{3-[3-(tert-butyl-dimethyl-silanyloxymethyl)-2-methoxy-pyridin-4-yl]-3-hydroxy-pentanoyl}-4-phenyl-oxazolidin-2-one), the resulting emulsion was extracted 7 times with 100 mL, in total 700 mL TBME. The aqueous phase was acidified with aqueous HCl in order to adjust pH 3.0 and extracted nine times with 100 mL, in total 900 mL dichloromethane/ethanol (4:1). After evaporation in a rotary evaporator (40° C., 5 mbar), the title product was obtained as a colorless semisolid (700 mg, 2.74 mmol, yield of 45% w/w, or 85% when calculated over the two steps) and in a purity of 89.2% as determined by HPLC (er=80.47:19.53, see Chiral HPLC method below).

Workup

  1. customthe ice bath was removed
  2. waitAfter 2 h (<0.2% area (R)-3-{3-[3-(tert-butyl-dimethyl-silanyloxymethyl)-2-methoxy-pyridin-4-yl]-3-hydroxy-pentanoyl}-4-phenyl-oxazolidin-2-one)
  3. extractionthe resulting emulsion was extracted 7 times with 100 mL
  4. extractionextracted nine times with 100 mL
  5. customAfter evaporation
  6. customin a rotary evaporator (40° C., 5 mbar)

Sources & evidence

ORD record
ord-eb022b6f16f444da8a723c07b6ea14cf
Source dataset
uspto-grants-2010_04
Patent number
US07705155B2

Reaction notes

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