Formaldehyde → 3-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-yn-1-ol

HRID 1506435ノート

反応式

HRID 1506435 の反応式
Br[C:2](Br)=[CH:3][C:4]1[C:8]([C:9]([F:12])([F:11])[F:10])=[C:7]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[O:6][N:5]=1.C([Li])CCC.CCCCCC.[CH2:31]=[O:32]>C1COCC1.CCOCC>[C:13]1([C:7]2[O:6][N:5]=[C:4]([C:3]#[C:2][CH2:31][OH:32])[C:8]=2[C:9]([F:12])([F:11])[F:10])[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

参加物

7

反応物 4

HCID 712FormaldehydeHCID 8058HexaneHCID 866699063-(2,2-Dibromovinyl)-5-phenyl-4-(trifluoromethyl)isoxazoleHCID 178418339Butyllithium

生成物 1

HCID 671673013-(5-Phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-yn-1-ol収率 63%

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

To a solution of 3-(2,2-dibromovinyl)-5-phenyl-4-(trifluoromethyl)isoxazole (Preparation 62A, 0.496 g, 1.19 mmol) in THF (6.0 mL) at −78° C. was slowly added a 2.5 M solution of butyl lithium in hexane (1.05 mL, 2.61 mmol). The reaction mixture was stirred at −78° C. for 25 min. and then warmed to room temperature gently with a heat gun. Once at room temperature, paraformaldehyde (0.713 g, 23.74 mmol) was added, and the reaction mixture was stirred for 5 min. The mixture was diluted with ether, washed with water (2×), and washed with brine. The combined aqueous layers were extracted with ether, and the combined organics layers were dried over anhydrous sodium sulfate and concentrated. The residue was purified by flash silica gel chromatography using a mixture of ethyl acetate in hexane (1%-5%-20%) to give 3-(5-phenyl-4-(trifluoromethyl)isoxazol-3-yl)prop-2-yn-1-ol (0.199 g, 0.745 mmol, 63% yield) as a yellowish-orange solid. The product had an HPLC ret. time=2.39 min.−Column: Chromolith SpeedROD 4.6×50 mm (4 min.); Solvent A=10% MeOH, 90% H2O, 0.1% TFA; Solvent B=90% MeOH, 10% H2O, 0.1% TFA. LC/MS M+1=268.17.

後処理

  1. temperaturewarmed to room temperature gently with a heat gun
  2. stirringthe reaction mixture was stirred for 5 min
  3. washwashed with water (2×)
  4. washwashed with brine
  5. extractionThe combined aqueous layers were extracted with ether
  6. dry with materialthe combined organics layers were dried over anhydrous sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by flash silica gel chromatography
  9. additiona mixture of ethyl acetate in hexane (1%-5%-20%)

出典と根拠

ORDレコード
ord-0350e825937a46ab9012da0a389bfa98
出典データセット
uspto-grants-2015_12
特許番号
US09216972B2

反応ノート

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