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Pyridine → 3-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1-(3-trifluoromethoxy-phenyl)-1,3-dihydro-indol-2-one

HRID 1297806
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HRID 1297806 반응식
[Si:1]([O:8][C:9]1[C:14]([CH3:15])=[CH:13][C:12]([C:16]2([OH:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[NH:18][C:17]2=[O:25])=[CH:11][C:10]=1[CH3:27])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[F:28][C:29]([F:41])([F:40])[O:30][C:31]1[CH:32]=[C:33](B(O)O)[CH:34]=[CH:35][CH:36]=1.N1C=CC=CC=1>ClCCl.C(OCC)(=O)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[C:4]([Si:1]([CH3:3])([CH3:2])[O:8][C:9]1[C:10]([CH3:27])=[CH:11][C:12]([C:16]2([OH:26])[C:24]3[C:19](=[CH:20][CH:21]=[CH:22][CH:23]=3)[N:18]([C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([O:30][C:29]([F:28])([F:40])[F:41])[CH:32]=3)[C:17]2=[O:25])=[CH:13][C:14]=1[CH3:15])([CH3:6])([CH3:5])[CH3:7]
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참가 물질

7

반응물 3

HCID 1049Pyridine2회HCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)2회HCID 589146893-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one

생성물 1

HCID 589147333-[4-(tert-Butyl-dimethyl-silanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1-(3-trifluoromethoxy-phenyl)-1,3-dihydro-indol-2-one수율 80.2%

시약·촉매·용매

3
HCID 8895Cupric acetate촉매2회HCID 6344Dichloromethane용매HCID 8857Ethyl Acetate용매

반응 조건

온도
32 °C

실험 절차

Using a method similar to Preparation 38, with 3-[4-(tert-Butyl-dimethylsilanyloxy)-3,5-dimethyl-phenyl]-3-hydroxy-1,3-dihydro-indol-2-one (15.34 g, 40 mmol), 3-(trifluoromethoxy)phenylboronic acid (16.47 g, 80 mmol), copper (II) acetate (7.27 g, 40 mmol), pyridine (6.5 ml, 80 mmol) and powdered 4A sieves (25 g) in dichloromethane (130 mL) and heat at 32° C. for 1 day stirring mechanically. Add more 3-(trifluoromethoxy)phenylboronic acid (8.24 g, 40 mmol), copper (II) acetate (3.64 g, 20 mmol), pyridine (6.5 ml, 80 mmol) and powdered 4A sieves (25 g) and continue heating for 1 day. Dilute with ethyl acetate (150 mL) and filter slowly through a pads of Celite and silica gel. After the filtration is complete stir the pads in additional ethyl acetate and refilter. Evaporate the organics in vacuo and apply the resulting residue to a silica pad with dichloromethane/acetone. Elute with 2% ethyl acetate/dichloromethane and concentrate in vacuo to obtain 17.45 g of a yellow solid. Titurate the solid in diethyl ether, filter, and dry to obtain 9.47 g (44%) of a white solid. MS (ES): m/z=526 (M+1−H2O); 1H NMR (DMSO-d6): δ7.71 (t, 1H), 7.58-7.52 (m, 3H), 7.32-7.25 (m, 2H), 7.13 (t, 1H), 7.01 (s, 2H), 6.87 (d, 1H), 6.76 (s, 1H), 2.14 (s, 6H), 0.99 (s, 9H), 0.17 (s, 6H).

후처리

  1. customsimilar to Preparation 38
  2. temperaturecontinue heating for 1 day
  3. filtrationfilter slowly through a pads of Celite and silica gel
  4. filtrationAfter the filtration
  5. stirringis complete stir the pads in additional ethyl acetate
  6. customEvaporate the organics in vacuo
  7. washElute with 2% ethyl acetate/dichloromethane
  8. concentrationconcentrate in vacuo

출처 및 근거

ORD 기록
ord-ec7064a55b8044588727b664b9f444b6
출처 데이터셋
uspto-grants-2007_07
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07250442B2

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