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

HRID 370354노트

반응식

HRID 370354 반응식
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]

참가 물질

5

반응물 3

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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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 2.5 M 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. 1 N 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) δ 7.22(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)102(s, 9H); 0.79-0.92(m, 4H)1; 0.27(s, 3H) 0.26(s, 3H). High resolution mass spec: calculated for C19H26NO2ClF3Si(M+H)+ : 420.1373, found: 420.1363.

후처리

  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

출처 및 근거

ORD 기록
ord-6f3779f48bc645fe86c6bdbc7683623e
출처 데이터셋
uspto-grants-2000_10
특허 번호
US06140499

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