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Potassium Carbonate → (R)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-3-methyl-1H-indole

HRID 717518
ノート
印刷プレビュー

反応式

HRID 717518 の反応式
CS(O[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([CH2:15][N:16]2[C:24]3[C:19](=[CH:20][C:21]([O:25][CH2:26][C:27]4[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=4)=[CH:22][CH:23]=3)[C:18]([CH3:33])=[C:17]2[C:34]2[CH:39]=[CH:38][C:37]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[CH:36][CH:35]=2)=[CH:11][CH:10]=1)(=O)=O.Cl.[F:49][CH2:50][C@@H:51]1[CH2:55][CH2:54][NH:53][CH2:52]1.C(=O)([O-])[O-].[K+].[K+]>C(#N)C>[CH2:26]([O:25][C:21]1[CH:20]=[C:19]2[C:24](=[CH:23][CH:22]=1)[N:16]([CH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][CH2:7][CH2:6][N:53]3[CH2:54][CH2:55][C@@H:51]([CH2:50][F:49])[CH2:52]3)=[CH:10][CH:11]=1)[C:17]([C:34]1[CH:35]=[CH:36][C:37]([O:40][CH2:41][C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)=[CH:38][CH:39]=1)=[C:18]2[CH3:33])[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
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 3

HCID 11430Potassium CarbonateHCID 893071282-(4-((5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-1-yl)methyl)phenoxy)ethyl methanesulfonateHCID 89619639(R)-3-(Fluoromethyl)pyrrolidine hydrochloride2 回

生成物 1

HCID 117774168(R)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-3-methyl-1H-indole

試薬・触媒・溶媒 1

HCID 6342
Acetonitrile
溶媒

反応条件

温度
80 °C

実験手順

A mixture of 2-(4-((5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-3-methyl-1H-indol-1-yl)methyl)phenoxy)ethyl methanesulfonate, (R)-3-(fluoromethyl)pyrrolidine (Intermediate 8) and potassium carbonate in acetonitrile was degassed with three vacuum/N2 cycles. The reaction was heated at 80° C. for 10 hrs, allowed to cool to room temperature and then diluted with water (40 mL). The aqueous layer was extracted with ethyl acetate (2×40 mL) and the combined ethyl acetate extracts were then washed with water (40 mL), washed with brine (40 mL), dried (MgSO4), filtered, concentrated and purified by silica gel chromatography (0%-5% MeOH in DCM) to give 274 mg of (R)-5-(benzyloxy)-2-(4-(benzyloxy)phenyl)-1-(4-(2-(3-(fluoromethyl)pyrrolidin-1-yl)ethoxy)benzyl)-3-methyl-1H-indole. 1H NMR (400 MHz, DMSO-d6): δ 7.48 (d, 4H), 7.44-7.37 (m, 4H), 7.37-7.32 (m, 2H), 7.30 (d, 2H), 7.21 (d, 1H), 7.15-7.10 (m, 3H), 6.81 (dd, 1H), 6.74 (s, 4H), 5.17-5.10 (m, 6H), 4.33-4.30 (m, 1H), 4.22-4.18 (m, 1H), 3.94 (t, 2H), 2.70 (t, 2H), 2.56-2.40 (m, 3H), 2.60 (t, 1H), 2.36-2.31 (m, 1H), 2.16 (s, 3H), 1.86-1.76 (m, 1H), 1.40-1.30 (m, 1H). LCMS: 655.3 (M+H)+.

後処理

  1. customwas degassed with three vacuum/N2 cycles
  2. temperatureto cool to room temperature
  3. additiondiluted with water (40 mL)
  4. extractionThe aqueous layer was extracted with ethyl acetate (2×40 mL)
  5. washthe combined ethyl acetate extracts were then washed with water (40 mL)
  6. washwashed with brine (40 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. custompurified by silica gel chromatography (0%-5% MeOH in DCM)

出典と根拠

ORDレコード
ord-73a5431a967e416481d2ab6505190689
出典データセット
uspto-grants-2015_11
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US09193714B2

反応ノート

読み込み中…

このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート