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

HRID 396396ノート

反応式

HRID 396396 の反応式
[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]

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 11673339Chlorotitaniumtriisopropoxide触媒HCID 1140Toluene溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-20 °C

実験手順

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).

後処理

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

出典と根拠

ORDレコード
ord-597858f11029412d96b31c6bd8ad78c2
出典データセット
uspto-grants-2003_08
特許番号
US06608087B1

反応ノート

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