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Ethanol → Ethyl 3-[2-fluoro-4-[[3-methoxy-4-(spiro[indene-1,4'-piperidine]-1'-ylmethyl)phenyl]methoxy]phenyl]propanoate

HRID 390404
ノート
印刷プレビュー

反応式

HRID 390404 の反応式
[NH:1]1[CH2:6][CH2:5][C:4]2([C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH:8]=[CH:7]2)[CH2:3][CH2:2]1.C(N(CC)C(C)C)(C)C.[CH2:24]([O:26][C:27](=[O:51])[CH2:28][CH2:29][C:30]1[CH:35]=[CH:34][C:33]([O:36][CH2:37][C:38]2[CH:43]=[CH:42][C:41]([CH2:44]Br)=[CH:40][C:39]=2C(F)(F)F)=[CH:32][C:31]=1[F:50])[CH3:25].C[CH2:53][OH:54]>>[F:50][C:31]1[CH:32]=[C:33]([O:36][CH2:37][C:38]2[CH:39]=[CH:40][C:41]([CH2:44][N:1]3[CH2:6][CH2:5][C:4]4([C:14]5[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=5)[CH:8]=[CH:7]4)[CH2:3][CH2:2]3)=[C:42]([O:54][CH3:53])[CH:43]=2)[CH:34]=[CH:35][C:30]=1[CH2:29][CH2:28][C:27]([O:26][CH2:24][CH3:25])=[O:51]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

5

反応物 4

HCID 702EthanolHCID 81531DiisopropylethylamineHCID 10330052Spiro[indene-1,4'-piperidine]HCID 670870493-[4-(4-Bromomethyl-2-trifluoromethyl-benzyloxy)-2-fluoro-phenyl]-propionic acid ethyl ester

生成物 1

HCID 58230595Ethyl 3-[2-fluoro-4-[[3-methoxy-4-(spiro[indene-1,4'-piperidine]-1'-ylmethyl)phenyl]methoxy]phenyl]propanoate収率 47.7%

反応条件

温度
80 °C

実験手順

To a solution of spiro[indene-1,4′-piperidine] (0.515 g, 2.58 mmol) in EtOH (15 mL) is added N,N-diisopropylethylamine (1.4 mL, 2.589 mmol) and 3-[4-(4-bromomethyl-2-trifluoromethyl-benzyloxy)-2-fluoro-phenyl]-propionic acid ethyl ester (1.1 g, 2.58 mmol) at room temperature and the reaction mixture is stirred for 16 hours at 80° C. The mixture is concentrated, diluted with water, and extracted with EtOAc (2×50 mL). The combined extracts are washed with water (20 mL) and saturated brine (20 mL), dried over Na2SO4, filtered, and concentrated. The crude material is purified by silica gel column chromatography to give the title compound as a colorless gel (0.650 g, 47.7%). 1H NMR (400 MHz, CDCl3) δ 7.42-7.35 (m, 2H), 7.31-7.29 (d, J=8 Hz, 1H), 7.20-7.01 (m, 3H), 7.05 (s, 1H), 7.01-6.99 (d, J=8 Hz, 1H), 6.64-6.93 (d, J=4 Hz, 1H), 6.86-6.83 (d, J=12 Hz, 1H) 6.77 (s, 1H), 5.05 (s, 2H), 4.03-3.98 (m, 2H), 3.79 (s, 3H), 3.57 (s, 2H), 2.89-2.86 (d, J=12 Hz, 2H), 2.79-2.76 (t, J=8 Hz, 2H), 2.55-2.53 (d, J=8 Hz, 2H), 2.41-2.35 (t, J=12 Hz, 2H), 2.10-2.05 (t, J=8 Hz, 2H), 1.22-1.17 (t, J=8 Hz, 3H).

後処理

  1. concentrationThe mixture is concentrated
  2. additiondiluted with water
  3. extractionextracted with EtOAc (2×50 mL)
  4. washThe combined extracts are washed with water (20 mL) and saturated brine (20 mL)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude material is purified by silica gel column chromatography

出典と根拠

ORDレコード
ord-af27012965a9453d8c17b126f75a5a9b
出典データセット
uspto-grants-2013_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08383642B2

反応ノート

読み込み中…

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