Chloride → Methyl 2-[4-[[2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl]methyl]phenyl]acetate

HRID 1508914ノート

反応式

HRID 1508914 の反応式
Cl[C:2]1[CH:7]=[C:6]([CH:8]2[CH2:10][CH2:9]2)[N:5]=[C:4]([C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=2)[N:3]=1.CC1(C)C(C)(C)OB([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([CH2:33][C:34]([O:36][CH3:37])=[O:35])=[CH:29][CH:28]=2)O1.C([O-])([O-])=O.[Na+].[Na+].[Cl-]>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].O.O1CCOCC1>[Cl:17][C:13]1[CH:12]=[C:11]([C:4]2[N:3]=[C:2]([CH2:26][C:27]3[CH:28]=[CH:29][C:30]([CH2:33][C:34]([O:36][CH3:37])=[O:35])=[CH:31][CH:32]=3)[CH:7]=[C:6]([CH:8]3[CH2:10][CH2:9]3)[N:5]=2)[CH:16]=[CH:15][CH:14]=1

参加物

8

反応物 4

HCID 312ChlorideHCID 10340Sodium CarbonateHCID 633553904-Chloro-2-(3-chlorophenyl)-6-cyclopropylpyrimidineHCID 674944814-(2-Methoxy-2-oxoethyl)benzylboronic Acid Pinacol Ester

生成物 1

HCID 90112009Methyl 2-[4-[[2-(3-chlorophenyl)-6-cyclopropylpyrimidin-4-yl]methyl]phenyl]acetate収率 52.6%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒HCID 312751,4-Dioxane溶媒

実験手順

A 20-mL sealed tube, with stirrer bar, was charged with 4-chloro-2-(3-chlorophenyl)-6-cyclopropylpyrimidine (0.365 g, 1.38 mol), methyl 2-(4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)phenyl)acetate (0.400 g, 1.38 mmol), Pd(dppf)Cl2 (0.113 g, 0.14 mmol), and powdered Na2CO3 (0.438 g, 4.14 mmol). Dioxane (6 mL) and water (3 mL) were added. The resulting mixture was stirred under Ar at 90° C. for 1.5 h until the starting chloride was consumed. After cooling to room temperature, the reaction mixture was filtered through celite washing with ethyl acetate until the filtrate was colorless. The aqueous layer was separated and the organic layer was washed with saturated sodium chloride (2×5 mL) then dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (95:5 to 1:2) as eluent to afford the title compound (0.285 g, 52%) as a colorless oil. MW=392.88. 1H NMR (DMSO-d6, 500 MHz) δ 8.30-8.27 (m, 2H), 7.59-7.51 (m, 2H), 7.31 (d, J=8.0 Hz, 2H), 7.28 (s, 1H), 7.21 (d, J=8.0 Hz, 2H), 4.07 (s, 2H), 3.64 (s, 2H), 3.59 (s, 3H), 2.16-2.09 (m, 1H), 1.16-1.05 (m, 4H); ESI MS m/z 393 [M+H]+.

後処理

  1. customA 20-mL sealed tube
  2. customwas consumed
  3. filtrationthe reaction mixture was filtered
  4. washthrough celite washing with ethyl acetate until the filtrate
  5. customThe aqueous layer was separated
  6. washthe organic layer was washed with saturated sodium chloride (2×5 mL)
  7. dry with materialthen dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was purified by chromatography on silica

出典と根拠

ORDレコード
ord-d4fb77e3c2d549c0b951caf44bc4dae3
出典データセット
uspto-grants-2015_12
特許番号
US09221843B2

反応ノート

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