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

HRID 646622ノート

反応式

HRID 646622 の反応式
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]

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-eb022b6f16f444da8a723c07b6ea14cf
出典データセット
uspto-grants-2010_04
特許番号
US07705155B2

反応ノート

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