Cesium fluoride → 3-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[3-(phenethoxymethyl)phenyl]pyridine

HRID 2095335ノート

反応式

HRID 2095335 の反応式
I[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:3]=1.[C:18]([O:22][C:23]([N:25]1[CH2:28][CH2:27][C@H:26]1[CH2:29][O:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35]([Sn](C)(C)C)[CH:36]=1)=[O:24])([CH3:21])([CH3:20])[CH3:19].[F-].[Cs+]>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:18]([O:22][C:23]([N:25]1[CH2:28][CH2:27][C@H:26]1[CH2:29][O:30][C:31]1[CH:32]=[N:33][CH:34]=[C:35]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([CH2:8][O:9][CH2:10][CH2:11][C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)[CH:3]=2)[CH:36]=1)=[O:24])([CH3:21])([CH3:19])[CH3:20]

参加物

7

反応物 3

HCID 25953Cesium fluorideHCID 105744715-Iodo-A-85380, 5-trimethylstannyl N-boc derivativeHCID 593714071-Iodo-3-(phenethoxymethyl)benzene

生成物 1

HCID 593715633-[[1-(tert-Butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-[3-(phenethoxymethyl)phenyl]pyridine収率 55%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418397HCID 178418397、化合物触媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

A solution/suspension of 1-iodo-3-(phenethoxymethyl)benzene (300 mg, 0.89 mmol, 1.0 equiv.), 3-[[1-(tert-butoxycarbonyl)-2(S)-azetidinyl]methoxy]-5-(trimethylstannyl)pyridine (380 mg, 0.89 mmol), CsF (271 mg, 1.78 mmol, 2.0 equiv.), CuI (17 mg, 0.09 mmol, 0.10 equiv.) and Pd(PPh3)4 (46 mg, 0.04 mmol, 0.05 equiv.) in anhydrous DMF (5 mL) was stirred for 5 h at 50° C. under nitrogen. The reaction progress was monitored by TLC (EtOAc/petroleum ether 1:1). The mixture was concentrated under vacuum, the residue was diluted with water and extracted with EtOAc (2×50 mL), and the combined organic layers were dried over Na2SO4. After concentration in vacuo, the residue was applied onto a silica gel column, which was eluted with EtOAc/petroleum ether/Et3N 3:6:0.5 to give the title compound (230 mg, 55%) as a yellow oil. 1H NMR (CDCl3, 300 MHz) δ 8.48 (s, 1H), 8.36 (d, J=2.1 Hz, 1H), 7.53-7.43 (m, 4H), 7.38 (s, 1H), 7.35-7.23 (m, 5H), 4.62 (s, 3H), 4.43 (s, 1H), 4.25 (dd, J=7.5, 3.0 Hz, 1H), 3.94 (t, J=7.5 Hz, 2H), 3.77 (t, J=7.5 Hz, 2H), 2.99 (t, J=7.2 Hz, 2H), 2.43-2.33 (m, 2H), 1.43 (s, 9H). LC-MS (ESI) m/z 475 (M+H+).

後処理

  1. concentrationThe mixture was concentrated under vacuum
  2. additionthe residue was diluted with water
  3. extractionextracted with EtOAc (2×50 mL)
  4. dry with materialthe combined organic layers were dried over Na2SO4
  5. concentrationAfter concentration in vacuo
  6. washwas eluted with EtOAc/petroleum ether/Et3N 3:6:0.5

出典と根拠

ORDレコード
ord-bb932e75dcb74bf4b15f54588805b25b
出典データセット
uspto-grants-2013_05
特許番号
US08445684B2

反応ノート

読み込み中…