Cesium fluoride → 1-(2-{4-[2-(3,5-Difluoro-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-azepane

HRID 1513872노트

반응식

HRID 1513872 반응식
[N:1]1([CH2:8][CH2:9][O:10][C:11]2[CH:37]=[CH:36][C:14]([O:15][C:16]3[C:25]4[C:20](=[CH:21][C:22]([O:26][CH3:27])=[CH:23][CH:24]=4)[CH:19]=[CH:18][C:17]=3OS(C(F)(F)F)(=O)=O)=[CH:13][CH:12]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[F-].[Cs+].[F:40][C:41]1(B(O)O)[CH:46]=[CH:45][CH:44]=[C:43]([F:47])[CH2:42]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1>C(#N)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:40][C:41]1[CH:46]=[C:45]([C:17]2[CH:18]=[CH:19][C:20]3[C:25](=[CH:24][CH:23]=[C:22]([O:26][CH3:27])[CH:21]=3)[C:16]=2[O:15][C:14]2[CH:13]=[CH:12][C:11]([O:10][CH2:9][CH2:8][N:1]3[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]3)=[CH:37][CH:36]=2)[CH:44]=[C:43]([F:47])[CH:42]=1

참가 물질

7

반응물 4

HCID 25953Cesium fluorideHCID 75806TricyclohexylphosphineHCID 57552539Trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-yl esterHCID 866265291,3-Difluoro-benzene boronic acid

생성물 1

HCID 114207081-(2-{4-[2-(3,5-Difluoro-phenyl)-6-methoxy-naphthalen-1-yloxy]-phenoxy}-ethyl)-azepane수율 99.3%

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 6342Acetonitrile용매2회

실험 절차

Dissolve trifluoromethanesulfonic acid 1-[4-(2-azepan-1-yl-ethoxy)-phenoxy]-6-methoxy-naphthalen-2-yl ester (435 mg, 0.80 mmol), cesium fluoride (864 mg, 5.7 mmol) and 1,3-difluoro-benzene boronic acid (383 mg, 2.4 mmol) in dry acetonitrile (5 mL) and stir for 10 minutes. In a separate flask suspend palladium acetate (18 mg, 0.08 mmol), and tricyclohexyl phosphine (33 mg, 0.12 mmol) in dry acetonitrile (15 mL) and sonicate under nitrogen for 10 minutes. Combine contents of both flasks and heat reaction at 60° C. for 15 minutes. Cool reaction and filter through celite and concentrate in vacuo. Purify crude product by silica gel chromatography using a 1-3% gradient of methanol in dichloromethane to yield 400 mg (98%) of the title compound: mass spectrum (ion spray) m/z=504.2 (M+H).

후처리

  1. customIn a separate flask suspend
  2. temperatureCombine contents of both flasks and heat
  3. customreaction at 60° C. for 15 minutes
  4. temperatureCool
  5. customreaction
  6. filtrationfilter through celite
  7. concentrationconcentrate in vacuo
  8. customPurify crude product by silica gel chromatography

출처 및 근거

ORD 기록
ord-c376f1a279cc483f84d210281bddb76b
출처 데이터셋
uspto-grants-2012_07
특허 번호
US08217032B2

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