1-Pentyne, 5-chloro- → (+/-)-2-(2-Amino-5-chloro-3-(t-butyldimethylsilyloxy)phenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol

HRID 363344ノート

反応式

HRID 363344 の反応式
Cl[CH2:2][CH2:3][CH2:4][C:5]#[CH:6].[Li]CCCC.[NH2:12][C:13]1[C:18]([O:19][Si:20]([C:23]([CH3:26])([CH3:25])[CH3:24])([CH3:22])[CH3:21])=[CH:17][C:16]([Cl:27])=[CH:15][C:14]=1[C:28](=[O:33])[C:29]([F:32])([F:31])[F:30]>C1COCC1>[NH2:12][C:13]1[C:18]([O:19][Si:20]([C:23]([CH3:26])([CH3:24])[CH3:25])([CH3:21])[CH3:22])=[CH:17][C:16]([Cl:27])=[CH:15][C:14]=1[C:28]([OH:33])([C:2]#[C:3][CH:4]1[CH2:6][CH2:5]1)[C:29]([F:32])([F:31])[F:30]

参加物

5

反応物 3

HCID 843081-Pentyne, 5-chloro-HCID 159230934-Chloro-2-trifluoroacetyl-6-(tert-butyldimethylsilyloxy)anilineHCID 178418339Butyllithium

生成物 1

HCID 11112583(+/-)-2-(2-Amino-5-chloro-3-(t-butyldimethylsilyloxy)phenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol収率 70.4%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

To a stirred, cooled (0° C.) solution of 31.8 mL (300 mmol) of 5-chloro-1-pentyne in 250 mL of THF was added 252 mL (630 mmol) of 2.5M n-BuLi in hexanes over 20 min. Over the course of the addition the internal temperature had warmed to ambient temperature, and the mixture was stirred at this temperature for 40 min. The reaction was cooled to -20° C. and treated with a solution of 32.7 g (97.4 mmol) of 2'-amino-5'-chloro-3'-(t-butyldimethylsilyloxy)-2,2,2-trifluoroacetophenone in 50 mL of THF over 10 min. The dark solution was stirred an additional 30 min. and the cold bath was removed. The reaction was stirred 5 min and poured into 800 mL of 0° C. 1N citric acid with rapid stirring. The mixture was extracted twice with ether, and the combined organic extracts were washed with water then brine, dried (MgSO4), and concentrated under reduced pressure. Chromatography on silica gel (elution with hexanes then 3:1 hexanes-ether) afforded 28.8 g (70%) of (±)-2-(2-amino-5-chloro-3-(t-butyldimethylsilyloxy)phenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol as an off-white solid, mp 125°-126° C. 1H NMR (300 MHz, CDCl3) δ7.22(d, 1H, J=2.2 Hz); 6.76(d, 1H, J=2.2 Hz); 4.86(br. s, 1H); 4.39(br. s, 2H); 1.32-1.43(m, 1H); 1.02(s, 9H); 0.79-0.92(m, 4H); 0.27(s, 3H); 0.26(s, 3H). High resolution mass spec: calculated for C19H26NO2ClF3Si(M+H)+ : 420.1373, found: 420.1363.

後処理

  1. additionOver the course of the addition the internal temperature
  2. temperatureThe reaction was cooled to -20° C.
  3. stirringThe dark solution was stirred an additional 30 min.
  4. customthe cold bath was removed
  5. stirringThe reaction was stirred 5 min
  6. additionpoured into 800 mL of 0° C
  7. extractionThe mixture was extracted twice with ether
  8. washthe combined organic extracts were washed with water
  9. dry with materialbrine, dried (MgSO4)
  10. concentrationconcentrated under reduced pressure
  11. washChromatography on silica gel (elution with hexanes

出典と根拠

ORDレコード
ord-70fddaf679af4a7a9f680e3a6539b7ce
出典データセット
uspto-grants-1999_02
特許番号
US05874430

反応ノート

読み込み中…