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

HRID 1513872ノート

反応式

HRID 1513872 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 6342Acetonitrile溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-c376f1a279cc483f84d210281bddb76b
出典データセット
uspto-grants-2012_07
特許番号
US08217032B2

反応ノート

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