Hydrochloric Acid → 5-[(R)-2-{[2-(3-Aminophenyl)ethyl]benzylamino}-1-(tert-butyl-dimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one

HRID 1039812노트

반응식

HRID 1039812 반응식
C([NH:20][C:21]1[CH:22]=[C:23]([CH2:27][CH2:28]OS(C2C=CC([N+]([O-])=O)=CC=2)(=O)=O)[CH:24]=[CH:25][CH:26]=1)(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH2:42]([NH:49][CH2:50][C@@H:51]([C:60]1[CH:69]=[CH:68][C:67]([O:70][CH2:71][C:72]2[CH:77]=[CH:76][CH:75]=[CH:74][CH:73]=2)=[C:66]2[C:61]=1[CH:62]=[CH:63][C:64](=[O:78])[NH:65]2)[O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(=O)(O)[O-].[Na+].Cl>C(#N)C.CCOC(C)=O.O>[NH2:20][C:21]1[CH:22]=[C:23]([CH2:27][CH2:28][N:49]([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:50][C@@H:51]([C:60]2[CH:69]=[CH:68][C:67]([O:70][CH2:71][C:72]3[CH:73]=[CH:74][CH:75]=[CH:76][CH:77]=3)=[C:66]3[C:61]=2[CH:62]=[CH:63][C:64](=[O:78])[NH:65]3)[O:52][Si:53]([C:56]([CH3:59])([CH3:58])[CH3:57])([CH3:55])[CH3:54])[CH:24]=[CH:25][CH:26]=1

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 516892Sodium Bicarbonate2회HCID 666727545-[(R)-2-benzylamino 1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-oneHCID 866469604-Nitrobenzenesulfonic Acid 2-[3-(Tritylamino)phenyl]ethyl Ester

생성물 1

HCID 667816275-[(R)-2-{[2-(3-Aminophenyl)ethyl]benzylamino}-1-(tert-butyl-dimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one수율 85.6%

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

실험 절차

A stirred mixture of 4-nitrobenzenesulfonic acid 2-[3-(tritylamino)phenyl]ethyl ester (7.44 g, 13.2 mmol); 5-[(R)-2-benzylamino-1-(tert-butyldimethylsilanyloxy)ethyl]-8-benzyloxy-1H-quinolin-2-one (5.42 g, 10.5 mmol) (see, e.g., U.S. Patent Publication No. 2006/0035931 A1, published Feb. 16, 2006) and sodium bicarbonate (3.32 g, 39.5 mmol) in acetonitrile (26.4 mL) was heated at 75° C. under nitrogen for 18 h. The mixture was cooled to room temperature and the pH was adjusted to pH<2 with aqueous hydrochloric acid (1 N, ˜40 mL). The mixture was stirred at room temperature for 1 h and then the pH of the mixture was adjusted to pH 7-8 with saturated aqueous sodium bicarbonate solution (˜30 mL). Water (˜50 mL) and EtOAc (˜50 mL) were added and the layers were separated (a small amount of dilute aqueous sodium chloride solution was added to improve separation). The aqueous layer was extracted with EtOAc (2×30 mL) and the combined organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (30-60% of EtOAc in hexanes) to give the title compound (5.7 g, 68% yield) as a light yellow foamy solid.

후처리

  1. customthe layers were separated (a small amount of dilute aqueous sodium chloride solution
  2. additionwas added
  3. customseparation)
  4. extractionThe aqueous layer was extracted with EtOAc (2×30 mL)
  5. dry with materialthe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel flash chromatography (30-60% of EtOAc in hexanes)

출처 및 근거

ORD 기록
ord-bc107376ccd54c07b04a2558bf0ebbaf
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08551978B2

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