Trifluoroacetic acid → HCID 71237033, 화합물

HRID 1045788노트

반응식

HRID 1045788 반응식
FC(F)(F)C(O)=O.[Si]([O:15][CH2:16][CH2:17][N:18]1[C:24]2[N:25]=[CH:26][CH:27]=[CH:28][C:23]=2[C:22]2[CH:29]=[CH:30][CH:31]=[CH:32][C:21]=2[C:20](=[N:33]O)[C:19]1=[O:35])(C(C)(C)C)(C)C>ClCCl.CO.[Zn]>[NH2:33][C@H:20]1[C:21]2[CH:32]=[CH:31][CH:30]=[CH:29][C:22]=2[C:23]2[CH:28]=[CH:27][CH:26]=[N:25][C:24]=2[N:18]([CH2:17][CH2:16][OH:15])[C:19]1=[O:35]

참가 물질

6

반응물 2

HCID 6422Trifluoroacetic acidHCID 86676259HCID 86676259, 화합물

생성물 1

HCID 71237033HCID 71237033, 화합물수율 71%

시약·촉매·용매 3

HCID 23994Zinc촉매HCID 887Methanol용매HCID 6344Dichloromethane용매

실험 절차

Add trifluoroacetic acid (124.0 mL, 1.64 mol) in several portions to a solution of 5-[2-(tert-butyl(dimethyl)silyl)oxyethyl]-7-hydroxyimino-pyrido[2,3-d][3]benzazepin-6-one (155.0 g, 389.9 mmol) in a mixture of dichloromethane (620 mL) and methanol (310 mL) in an ambient temperature water bath. Add zinc (76.5 g, 1.2 mol) in several portions so that internal temperature was maintained at 33-38° C. Stir for 15 hours at ambient temperature. Filter mixture through Celite®, wash with 10% methanol/dichloromethane (100 mL) and concentrate the filtrate. Add dichloromethane (0.5 L) and ice (500 g), stir and basify with a 50% aqueous solution of NaOH. Filter out solids, separate filtrate layers. Extract from aqueous with dichloromethane (2×100 mL), and concentrate combined organics. Slurry solids in hexane, and then filter and dry under high vacuum to obtain the racemate of the title compound as a light yellow solid (74.0 g, 274.8 mmol, 71%). Purify the material on a Chiralpak® AD column eluting with ethanol (0.2% dimethethylamine): acetonitrile (0:100 to 100:0) to obtain the title compound (35.0 g, 130 mmol, 33.3%) as a white solid. MS (m/z): 270 (M+1); [α]Na25=+187.83° (c=6.9, methanol).

후처리

  1. filtrationFilter mixture through Celite®
  2. washwash with 10% methanol/dichloromethane (100 mL)
  3. concentrationconcentrate the filtrate
  4. stirringAdd dichloromethane (0.5 L) and ice (500 g), stir
  5. filtrationFilter out solids
  6. customseparate filtrate layers
  7. extractionExtract from aqueous with dichloromethane (2×100 mL)
  8. concentrationconcentrate
  9. filtrationSlurry solids in hexane, and then filter
  10. customdry under high vacuum

출처 및 근거

ORD 기록
ord-445df6e63e8a4fa5b4eee5d9f9bf00fa
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08569286B2

반응 노트

불러오는 중…