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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
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HRID 604148 반응식
[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]
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참가 물질

9

반응물 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

생성물 1

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

시약·촉매·용매 4

HCID 67553Tetrabutylammonium Iodide촉매HCID 167845palladium(II) acetate촉매HCID 1140Toluene용매HCID 57417360Sodium chloride; water용매

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온도
85 °C

실험 절차

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]+

후처리

  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)

출처 및 근거

ORD 기록
ord-b7a1318d9c7846d9a3d828b222c0d279
출처 데이터셋
uspto-grants-2011_03
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07906517B2

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