Sodium Carbonate → Methyl 2-(4-((2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetate

HRID 1508903ノート

反応式

HRID 1508903 の反応式
Cl[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([O:12][CH:13]2[CH2:17][CH2:16][CH2:15][CH2:14]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+].O1CCOCC1>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>[CH:13]1([O:12][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]([C:8]([F:11])([F:10])[F:9])[N:5]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1

参加物

7

反応物 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 674944814-(2-Methoxy-2-oxoethyl)benzylboronic Acid Pinacol EsterHCID 901131284-Chloro-2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidine

生成物 1

HCID 90111569Methyl 2-(4-((2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetate収率 67%

試薬・触媒・溶媒 2

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

反応条件

温度
90 °C

実験手順

A 20-mL sealed tube, with stirrer bar, was charged with 4-chloro-2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidine (0.400 g, 1.50 mol), methyl 2-(4-((4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)methyl)phenyl)acetate (0.478 g, 1.65 mmol), Pd(dppf)Cl2 (0.122 g, 0.15 mmol), and powdered Na2CO3 (0.477 g, 4.50 mmol). Dioxane (8 mL) and water (4 mL) were added. The resulting mixture was stirred under Ar at 90° C. for 2.5 h. After this time, the mixture was cooled to room temperature and 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 (2×10 mL) then dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (10:0 to 3:1) as eluent to afford the title compound (0.40 g, 67%) as a yellow oil. MW=394.39. 1H NMR (CDCl3, 300 MHz) δ 7.25 (s, 4H), 7.14 (s, 1H), 5.46 (septet, J=3.0 Hz, 1H), 4.08 (s, 2H), 3.69 (s, 3H), 3.62 (s, 2H), 2.04-1.73 (m, 6H), 1.72-1.56 (m, 2H); ESI MS m/z 327 [M-C5H9+2H]+.

後処理

  1. customA 20-mL sealed tube
  2. temperatureAfter this time, the mixture was cooled to room temperature
  3. filtrationfiltered
  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 (2×10 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-8fd3d5c987db4a61a7f4881ae893a2cb
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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