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

HRID 1508903Notes

Reaction equation

HRID 1508903 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

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

Conditions

Temperature
90 °C

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-8fd3d5c987db4a61a7f4881ae893a2cb
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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