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Binap, (A+-)- → Tert-butyl 4-{2-[(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate

HRID 604148
ノート
印刷プレビュー

反応式

HRID 604148 の反応式
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][C:11]=2[CH2:20][NH2:21])[CH:9]=1)([CH3:3])[CH3:2].Cl[C:25]1[N:30]=[CH:29][C:28]([O:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:27][N:26]=1.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC.[Cl-].[Na+].O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([O:22][CH3:23])=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:12][C:11]=2[CH2:20][NH:21][C:25]2[N:26]=[CH:27][C:28]([O:31][CH2:32][CH2:33][CH2:34][C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=[CH:29][N:30]=2)[CH:9]=1)([CH3:3])[CH3:2]
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

9

反応物 4

HCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 57556051Tert-butyl 4-(2-chloro-pyrimidin-5-yloxy)-butyrateHCID 591351271-[5'-Isopropyl-2'-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methanamine

生成物 1

HCID 66603218Tert-butyl 4-{2-[(5'-isopropyl-2'-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate
収率 33.6%

試薬・触媒・溶媒 4

HCID 67553Tetrabutylammonium Iodide触媒HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒HCID 57417360Sodium chloride; water溶媒

反応条件

温度
85 °C

実験手順

C-(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-yl)-methylamine (1.54 g) is dissolved in toluene (25 ml), and thereto are added tert-butyl 4-(2-chloro-pyrimidin-5-yloxy)-butyrate (1.96 g), palladium acetate (II) (195 mg), (±)-2,2′-bis(diphenylphosphino)-1,1′-binaphthalene (543 mg), tetra-n-butyl ammonium iodide (359 mg) and sodium tert-butoxide (560 mg), and the mixture is stirred under nitrogen flow at 85° C. overnight. The reaction solution is allowed to cool to room temperature, and thereto is added a saturated brine, and the mixture is extracted with ethyl acetate, and the organic layer is dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=47:3→3:1) to give tert-butyl 4-{2-[(5′-isopropyl-2′-methoxy-4-trifluoromethyl-biphenyl-2-ylmethyl)-amino]-pyrimidin-5-yloxy}-butyrate (895 mg). MS (m/z): 560 [M+H]+

後処理

  1. temperatureto cool to room temperature
  2. extractionthe mixture is extracted with ethyl acetate
  3. dry with materialthe organic layer is dried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue is purified by silica gel column chromatography (hexane:ethyl acetate=47:3→3:1)

出典と根拠

ORDレコード
ord-b7a1318d9c7846d9a3d828b222c0d279
出典データセット
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US07906517B2

反応ノート

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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