2-Thiophenecarboxaldehyde → 3-Hydroxy-2-methyl-2-phenoxy-3-thiophen-2-yl-propionic Acid

HRID 1393478ノート

反応式

HRID 1393478 の反応式
[Li+].CC([N-]C(C)C)C.C1COCC1.CCCCCCC.C(C1C=CC=CC=1)C.[O:29]([CH:36]([CH3:40])[C:37]([OH:39])=[O:38])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.[S:41]1[CH:45]=[CH:44][CH:43]=[C:42]1[CH:46]=[O:47]>C1COCC1.CCCCCC.CCOCC>[OH:47][CH:46]([C:42]1[S:41][CH:45]=[CH:44][CH:43]=1)[C:36]([CH3:40])([O:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:37]([OH:39])=[O:38]

参加物

8

反応物 4

HCID 73642-ThiophenecarboxaldehydeHCID 13658DL-2-Phenoxypropionic acidHCID 2724682Lithium diisopropylamideHCID 22742125Tetrahydrofuran heptane ethylbenzol

生成物 1

HCID 223400803-Hydroxy-2-methyl-2-phenoxy-3-thiophen-2-yl-propionic Acid収率 97.1%

試薬・触媒・溶媒 3

HCID 3283Diethyl Ether溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒

実験手順

To a 2.0 M solution of LDA in THF/heptane/ethyl benzene (200 mL, 408 mmol) cooled by an ice/acetone bath, a 0.75 M solution of 2-phenoxypropionic acid (30.8 g, 185 mmol) in THF (250 mL) was added dropwise over 30 min, keeping the reaction temperature below −10° C. After allowing the reaction mixture to stir for 15 min, a 0.75 M solution of 2-thiophenecarboxaldehyde (20.8 g, 185 mmol) in THF (250 mL) was added dropwise over the course of 1 h, maintaining the reaction temperature below −5° C. After stirring for 5 min at 0° C., HPLC analysis showed the reaction to be complete. The reaction was poured into ice water (600 mL) and ether (500 mL) was added. Hexane (1.0 L) was added and the layers were separated. The aqueous layer was further extracted with Et2O:hexane (1:2) (750 mL). The organic layers were checked for product then discarded. Ethyl acetate (500 mL) was added to the aqueous layer, acidified to pH=2 with conc. HCl (18 mL), and the layers were separated. The aqueous layer was extracted with ethyl acetate (2×200 mL). The organic layer was dried over NaCl and solvent removed in vacuo to provide 50.0 g of crude product. The product was used in the next step without further purification: 1H NMR (400 MHz, CDCl3) δ 7.33 (dd, 1 H), 7.26 (m, 2 H), 7.12 (m, 1 H), 7.04 (d, 1 H), 6.97 (m, 2 H), 6.87 (dd, 1 H), 5.37 (s, 1 H), 1.40 (s, 3 H); MS (EI−) 277.1 (M−1)−.

後処理

  1. customthe reaction temperature below −10° C
  2. temperaturemaintaining the reaction temperature below −5° C
  3. stirringAfter stirring for 5 min at 0° C.
  4. customthe reaction
  5. additionwas added
  6. customthe layers were separated
  7. extractionThe aqueous layer was further extracted with Et2O:hexane (1:2) (750 mL)
  8. additionEthyl acetate (500 mL) was added to the aqueous layer
  9. customthe layers were separated
  10. extractionThe aqueous layer was extracted with ethyl acetate (2×200 mL)
  11. dry with materialThe organic layer was dried over NaCl and solvent
  12. customremoved in vacuo

出典と根拠

ORDレコード
ord-74df8b30d3684439bc21205e25f53731
出典データセット
uspto-grants-2008_03
特許番号
US07345070B2

反応ノート

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