Acetic Acid → Ethyl 2-(4-ethynylpyrimidin-5-yl)acetate

HRID 1485246Notes

Reaction equation

HRID 1485246 reaction equation
C([Si]([C:8]#[C:9][C:10]1[C:15]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:14][N:13]=[CH:12][N:11]=1)(CC)CC)C.C(O)(=O)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C([O-])(O)=O.[Na+]>C1COCC1.C(Cl)Cl>[C:9]([C:10]1[C:15]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:14][N:13]=[CH:12][N:11]=1)#[CH:8]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 68282515Ethyl 2-(4-((triethylsilyl)ethynyl)pyrimidin-5-yl)acetate

Product 1

HCID 86675727Ethyl 2-(4-ethynylpyrimidin-5-yl)acetateYield 54%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-(4-((triethylsilyl)ethynyl)pyrimidin-5-yl)acetate (I109) (1.174 g, 3.856 mmol) in dry THF (40 mL) under an atmosphere of nitrogen was added acetic acid (0.243 mL, 4.24 mmol) followed by TBAF (1.0 M in THF, 4.049 mL, 4.049 mmol) dropwise at 0° C. The reaction was stirred at this temperature for 5 minutes and was then poured into sat. aq. NaHCO3 (100 mL) and DCM (100 mL). The layers were separated and the aqueous layer was extracted with DCM (2×100 mL). The combined organics were washed with water (100 mL), brine (100 mL), dried (MgSO4), filtered and concentrated in vacuo to give a brown oil. The crude material was purified by silica gel chromatography (Isolera Biotage, 40 g Si Cartridge, 0-60% EtOAc in petroleum benzine 40-60° C.) to give the title compound (I110) (0.397 g, 54% yield) as a brown oil; 1H NMR (400 MHz, CDCl3) δ 9.11 (s, 1H), 8.72 (s, 1H), 4.20 (q, J=7.1 Hz, 2H), 3.81 (s, 2H), 3.56 (s, 1H), 1.27 (t, J=7.1 Hz, 3H). LCMS Method C: rt 4.78 min; m/z 191.1 [M+H]+.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with DCM (2×100 mL)
  3. washThe combined organics were washed with water (100 mL), brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto give a brown oil
  8. customThe crude material was purified by silica gel chromatography (Isolera Biotage, 40 g Si Cartridge, 0-60% EtOAc in petroleum benzine 40-60° C.)

Sources & evidence

ORD record
ord-5ccb1e51a2b04a358e4f9368de440264
Source dataset
uspto-grants-2016_08
Patent number
US09421205B2

Reaction notes

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