Ethyl oxoacetate → 2-Hydroxy-3-methyl-4-oxo-4-(2-phenyl-thiazol-5-yl)-butyric Acid Ethyl Ester

HRID 585109

반응식

HRID 585109 반응식
[C:1]1([C:7]2[S:8][C:9]([C:12](=[O:15])[CH2:13][CH3:14])=[CH:10][N:11]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:26]([O:30][CH2:31][CH3:32])(=[O:29])[CH:27]=[O:28]>O1CCCC1.C1(C)C=CC=CC=1.CC(C)[O-].CC(C)[O-].CC(C)[O-].Cl[Ti+3]>[CH2:31]([O:30][C:26](=[O:29])[CH:27]([OH:28])[CH:13]([CH3:14])[C:12](=[O:15])[C:9]1[S:8][C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[N:11][CH:10]=1)[CH3:32]

참가 물질

7

반응물 3

HCID 70211Ethyl oxoacetateHCID 2733832Lithium HexamethyldisilazideHCID 98559161-(2-Phenyl-thiazol-5-yl)-propan-1-one

생성물 1

HCID 99015872-Hydroxy-3-methyl-4-oxo-4-(2-phenyl-thiazol-5-yl)-butyric Acid Ethyl Ester수율 195.7%

시약·촉매·용매 3

HCID 11673339Chlorotitaniumtriisopropoxide촉매HCID 1140Toluene용매HCID 8028Tetrahydrofuran용매

반응 조건

온도
-20 °C

실험 절차

To a −78° C. solution of 0.26 g (1.2 mmol) of the above-prepared 1-(2-phenyl-thiazol-5-yl)-propan-1-one was added 0.24 g (1.4 mmol) of 1M lithium bis(trimethylsilyl)amide in tetrahydrofuran. The mixture was allowed to stir for 0.5 hours and then 0.38 g (1.5 mmol) of 1M chlorotitanium triisopropoxide in hexanes was added. The reaction was allowed to warm to −20° C. and stirred for 15 minutes. The reaction was recooled to −78° C. and 0.25 g (0.24 mmol) of ethyl glyoxalate in toluene (50%) was added. The solution was warmed to room temperature and allowed to stir for 0.5 hours. The reaction was quenched with aqueous potassium sodium tartrate tetrahydrate and partitioned with ethyl acetate. The organic phase was twice washed with aqueous potassium sodium tartrate tetrahydrate, once with water, once with brine and dried over sodium sulfate. The solvent was evaporated under reduced pressure and the residue was purified by chromatography on silica gel using 1:9 ethyl acetate:hexanes to give 0.15 g of the title compound (40%). 1H NMR (500 MHz, CDCl3) δ 8.42 (s, 1H) 8.01 (d, 2H) 7.48 (m, 3H) 5.8 (m, 1H) 4.27 (q, 2H) 3.75 (m, 1H) 3.28 (m, 1H) 1.37 (d, 3H) 1.26 (t, 3H).

후처리

  1. stirringstirred for 15 minutes
  2. customwas recooled to −78° C.
  3. temperatureThe solution was warmed to room temperature
  4. stirringto stir for 0.5 hours
  5. customThe reaction was quenched with aqueous potassium sodium tartrate tetrahydrate
  6. custompartitioned with ethyl acetate
  7. washThe organic phase was twice washed with aqueous potassium sodium tartrate tetrahydrate, once with water, once with brine
  8. dry with materialdried over sodium sulfate
  9. customThe solvent was evaporated under reduced pressure
  10. customthe residue was purified by chromatography on silica gel using 1:9 ethyl acetate

출처 및 근거

ORD 기록
ord-5f40d6d28d1a40dc867290315c5c9d59
출처 데이터셋
uspto-grants-2005_08
특허 번호
US06930116B2

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