trans-Crotonyl chloride → Locostatin

HRID 133162

反応式

HRID 133162 の反応式
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Li]CCCC.[C:19](Cl)(=[O:23])/[CH:20]=[CH:21]/[CH3:22]>C1COCC1.CCOCC>[C:19]([N:9]1[C@@H:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:12][O:11][C:10]1=[O:13])(=[O:23])/[CH:20]=[CH:21]/[CH3:22]

参加物

6

反応物 3

HCID 643131trans-Crotonyl chlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 178418339Butyllithium

生成物 1

HCID 5702600Locostatin収率 109.2%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒

反応条件

温度
-78 °C

実験手順

A solution of (4S)-4-benzyl-2-oxazolidinone (1.0 g, 5.6 mmol) in anhydrous THF (20 ml) was cooled to −78° C. n-BuLi (1.6 M solution in hexanes, 3.5 ml, 5.6 mmol) was added dropwise to the cooled solution. After 30 minutes, crotonyl chloride (0.59 ml, 6.2 mmol) was added to the mixture. The reaction was stirred for 30 minutes at −78° C., then warmed slowly to room temperature. The reaction mixture was quenched by addition of 4 ml saturated aqueous ammonium chloride. The resultant reaction mixture was diluted with ether, and washed with water and brine. The organic layer was dried using anhydrous Na2SO4 and evaporated under reduced pressure. Flash chromatography on a silica gel column using ethyl acetate/hexane (1/3) as eluent provided compound 1, i.e., (4S)-3-((E)-2-butenoyl)-4-benzyl-2-oxazolidinone, (1.50 g, 87%) as a white solid. m.p.: 83° C. IR (KBr): 3027, 2922, 2539, 1772, 1682, 1351, 1209 cm−1. 1H NMR (400 MHz, CDCl3): 7.36-7.15 (m, 7H, aromatic H's, CH═CH); 4.75-4.70 (m, 1H, CHN); 4.23-4.15 (m, 2H, CH2O); 3.33 (dd, 1H, J=3.3, 13.4 Hz, CHHPh); 2.79 (dd, 1H, J=9.5, 13.4 Hz, CHHPh); 1.98 (dd, 3H, J=1.0, 6.2 Hz, CH3). 13C NMR (100 MHz, CDCl3): δ 164.69, 153.51, 146.95, 135.28, 129.37, 128.86, 127.23, 121.74, 66.01, 55.20, 37.79, 18.50.

後処理

  1. additionwas added dropwise to the cooled solution
  2. temperaturewarmed slowly to room temperature
  3. customThe reaction mixture was quenched by addition of 4 ml saturated aqueous ammonium chloride
  4. customThe resultant reaction mixture
  5. washwashed with water and brine
  6. customThe organic layer was dried
  7. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-beab3f4b89724e0ab8c4a610b651d35b
出典データセット
uspto-grants-2008_06
特許番号
US07390826B2

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