Ethyl Acetate → HCID 178502377、化合物

HRID 1776014ノート

反応式

HRID 1776014 の反応式
[CH3:1][O:2][C:3](=[O:28])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].CC1(C)C(C)(C)OB([C:37]2[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=O)C>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:1][O:2][C:3](=[O:28])[NH:4][C@H:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[C:16]1[NH:17][CH:18]=[C:19]([C:21]2[CH:26]=[CH:25][C:24]([C:37]3[CH:43]=[CH:42][C:40]([NH2:41])=[CH:39][CH:38]=3)=[CH:23][CH:22]=2)[N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7]

参加物

7

反応物 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 178502354HCID 178502354、化合物

生成物 1

HCID 178502377HCID 178502377、化合物収率 75%

試薬・触媒・溶媒 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 218864351,4-Dioxane--water (1/1)溶媒

実験手順

To a solution of ((S)-1-{(S)-2-[4-(4-bromo-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (9.10 g, 20.34 mmol) in dioxane:water (3:1) (200 mL), was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (4.9 g, 22.37 mmol), sodium carbonate (4.3 g, 40.68 mmol) and Pd(dppf)2Cl2 (0.83 g, 5%). The reaction mixture was warmed to reflux under nitrogen, stirred for 4 h, cooled to RT, filtered, and concentrated. The residue was extracted with ethyl acetate and water, dried with sodium sulfate and concentrated. The crude product was purified by silica gel chromatography eluting with 1:1 hexane:ethyl acetate, to provide the title compound (7 g, 75% yield) as a yellow solid. 1H NMR (CDCl3, 400 MHz) δ (ppm) 7.62-7.55 (m, 1H), 7.50 (d, J=8.0 Hz, 2H), 7.40 (m, 3H), 7.18 (s, 1H), 6.75 (d, J=8.4 Hz, 2H), 5.50 (d, J=9.2 Hz, 1H), 5.25-5.23 (m, 1H), 4.31 (t, J=2.4 Hz, 1H), 3.83-3.80 (m, 1H), 3.67 (s, 3H), 3.59-3.53 (m, 1H), 3.05-2.95 (m, 1H), 2.40-2.30 (m, 1H), 2.19-2.11 (m, 1H), 2.08-2.03 (m, 1H), 1.98-1.93 (m, 1H), 1.07-1.01 (m, 1H), 0.85 (d, J=6.8 Hz, 6H).

後処理

  1. temperatureThe reaction mixture was warmed
  2. temperatureto reflux under nitrogen
  3. filtrationfiltered
  4. concentrationconcentrated
  5. extractionThe residue was extracted with ethyl acetate and water
  6. dry with materialdried with sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by silica gel chromatography
  9. washeluting with 1:1 hexane

出典と根拠

ORDレコード
ord-5b7877f70d3c430da0ee9e65742975f7
出典データセット
uspto-grants-2016_02
特許番号
US09260414B2

反応ノート

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