Hydrogen Peroxide → (R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid

HRID 1945045

반응식

HRID 1945045 반응식
C([C@H]1COC(=O)N1[C:14](=[O:37])[C@H:15]([CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:27][CH:26]=1)[CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])C1C=CC=CC=1.C1COCC1.OO.[Li+].[OH-:46]>O>[C:28]1([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)[CH:29]=[CH:30][C:25]([CH2:24][C@H:15]([CH2:16][C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:14]([OH:37])=[O:46])=[CH:26][CH:27]=1

참가 물질

6

반응물 4

HCID 784Hydrogen PeroxideHCID 3939Lithium HydroxideHCID 8028TetrahydrofuranHCID 59607858(R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate

생성물 1

HCID 59607655(R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid수율 93.6%

시약·촉매·용매 1

HCID 962Water용매

실험 절차

To a stirred solution of (R)-tert-butyl 4-((S)-4-benzyl-2-oxooxazolidin-3-yl)-3-(biphenyl-4-ylmethyl)-4-oxobutanoate (1.20 g, 2.402 mmol) in a mixed solvent of THF (20 mL) and water (5 mL), a solution of aqueous H2O2 (0.960 mL, 9.61 mmol) and aqueous LiOH (4.80 ml, 4.80 mmol) is added at 0° C. during 5 minutes. After stirring for 1.5 hour, the reaction is quenched with saturated aqueous Na2SO3 (10 mL) at 0° C., and allowed to stir for 10 minutes at the same temperature. The reaction mixture is warmed up to ambient temperature while stirring for 0.5 hour. Then, saturated aqueous NaHCO3 and brine are added to the mixture. The product is extracted with ethyl acetate, washed with aqueous 1M HCl, dried over MgSO4, filtered, and concentrated under reduced pressure. The obtained residue is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=75:25 to 0:100) to give (R)-2-(biphenyl-4-ylmethyl)-4-tert-butoxy-4-oxobutanoic acid (765 mg, 93%). HPLC retention time=1.63 minutes (condition D); MS=338.6 (m−1); 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.43 (s, 9H) 2.41 (A of ABX, Jab=16.67 Hz, Jax=4.55 Hz, 1H) 2.52-2.67 (B of ABX, Jab=16.75 Hz, Jbx=8.45 Hz, 1H) 2.74-2.89 (m, 1H) 3.06-3.22 (m, 2H) 7.22-7.29 (m, 2H) 7.30-7.37 (m, 1H) 7.43 (t, J=7.58 Hz, 2H) 7.53 (d, J=8.1 Hz, 2H) 7.57 (d, J=7.8 Hz, 2H).

후처리

  1. customthe reaction is quenched with saturated aqueous Na2SO3 (10 mL) at 0° C.
  2. stirringto stir for 10 minutes at the same temperature
  3. stirringwhile stirring for 0.5 hour
  4. additionThen, saturated aqueous NaHCO3 and brine are added to the mixture
  5. extractionThe product is extracted with ethyl acetate
  6. washwashed with aqueous 1M HCl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe obtained residue is purified by flash column chromatography on 120 g of silica gel (heptane/EtOAc=75:25 to 0:100)

출처 및 근거

ORD 기록
ord-ccdd9b8d145e428a86acba14e3d193cc
출처 데이터셋
uspto-grants-2013_03
특허 번호
US08394853B2

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