Potassium Carbonate → ethyl 7-(pyridin-3-ylcarbonyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 854884Notes

Reaction equation

HRID 854884 reaction equation
I[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23](B(O)O)[CH:22]=1.[C:30]([O-])([O-])=[O:31].[K+].[K+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[N:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:30]([C:2]2[CH:11]=[C:10]3[C:5]([CH:6]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:8]([C:12]([F:15])([F:14])[F:13])[O:9]3)=[CH:4][CH:3]=2)=[O:31])[CH:22]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27343783-Pyridinylboronic acidHCID 69517680ethyl 7-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 69525368ethyl 7-(pyridin-3-ylcarbonyl)-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 4.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

The ethyl 7-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylate from Example 9a, Step 2 (1.0 g, 2.51 mmol), pyridin-3-ylboronic acid (0.34g, 2.76 mmol), K2CO3 (1.04 g, 7.53 mmol), and PdCl2(PPh3)2 (53 mg, 0.075 mmol) were mixed in dioxane (10 mL) in a sterling bomb. The reactor was charged withcarbon monoxide (40 psi). The reaction was heated to 80° C. for 6 h then room temperature overnight. After filtration, the reaction was quenched with NH4Cl and extracted with EtOAc. The organic layer was washed and dried over MgSO4. The filtrate was evaporated and dried in vacuo to afford crude which was purified by RPHPLC with 50 to 95% ACN in water to give yellow solid (39 mg, 4%): LCMS m/z 378.10 (M+H). 1H NMR (CDCl3/400 MHz) 9.08 (s, 1H), 8.97 (d, 1H, J=5.2 Hz), 8.48 (d, 1H, J=8.0 Hz), 7.81 (dd, 1H, J=7.6, 5.2 Hz), 7.75 (s, 1H), 7.40 (m, 3H), 5.76 (q, 1H, J=6 Hz), 4.34 (m, 2H), 1.36 (t, 3H, J=7.2 Hz).

Workup

  1. customroom temperature overnight
  2. filtrationAfter filtration
  3. customthe reaction was quenched with NH4Cl
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed
  6. dry with materialdried over MgSO4
  7. customThe filtrate was evaporated
  8. customdried in vacuo
  9. customto afford crude which
  10. customwas purified by RPHPLC with 50 to 95% ACN in water

Sources & evidence

ORD record
ord-36fa0f8f2c4b42c19dce44ee437be7c0
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

Loading…