Potassium Carbonate → ethyl 6-chloro-5-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855147

Reaction equation

HRID 855147 reaction equation
[IH:1].[Cl:2][C:3]1[C:4](N)=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][CH:8]([C:13]([F:16])([F:15])[F:14])[C:7]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:6]2.N([O-])=O.[K+].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[Cl:2][C:3]1[C:4]([I:1])=[C:5]2[C:10](=[CH:11][CH:12]=1)[O:9][CH:8]([C:13]([F:16])([F:15])[F:14])[C:7]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:6]2

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 24841Hydrogen iodideHCID 516910Potassium nitriteHCID 58934551ethyl 6-chloro-5-amino-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 58934962ethyl 6-chloro-5-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 49%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

To a solution of 47% aqueous HI (11 mL, 59 mmol) dissolved in DMSO (11 mL) was added dropwise at 35° C. a solution of ethyl 6-chloro-5-amino-2-(trifluoromethyl)-2H-chromene-3-carboxylate (3.8 g, 11.8 mmol) in a mixture of 11 mL of DMSO and potassium nitrite (1.63 g, 23.6 mmol) with stirring. The resulted mixture was stirred at 35° C. for 15 min, and then it was transferred into 150 mL of a solution of potassium carbonate (10 g) in ice water. The product was extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium carbonate, 5% aqueous sodium hydrosulfite, and brine, dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on silica gel column with 1:9 EtOAc/hexane. The product was obtained as 2.5 g light yellow solid. A small amount of the product was further purified on reverse phase HPLC. It gave an off-white solid. m.p=117.0-119.0° C. LC-MS (ES+): 433.2(M+1, 100); 1H NMR(CDCl3/400 MHz) 7.93(s,1H), 7.36(d, J=8.4 Hz, 1H), 6.91(d, J=8.4 Hz, 1H), 5.65(q, J=6.8 Hz, 1H), 4.33(m, 2H), 1.36(t, J=6.8 Hz, 3H). 19F NMR(CDCl3/400 Hz) −78.50(d, J=6.8 Hz). 13C NMR (CDCl3/400 MHz) 163.3, 152.3, 140.9, 133.6, 132.2, 124.7, 123.2(q, J=287.7 Hz), 119.4, 117.6, 104.5, 70.3(q, J=33.4 Hz), 62.0, 14.4. MS(EI+) 432.0(M+, 20), 363.0(M-CF3, 100). High resolution MS(EI+) m/z calc. for Cl3H9ClF3IO3: 431.9271 (M+), found: 431.9238.

Workup

  1. stirringThe resulted mixture was stirred at 35° C. for 15 min
  2. extractionThe product was extracted with ethyl acetate
  3. washThe combined organic extracts were washed with saturated aqueous sodium carbonate, 5% aqueous sodium hydrosulfite, and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customAfter removing the solvent
  6. customthe residue was purified on silica gel column with 1:9 EtOAc/hexane

Sources & evidence

ORD record
ord-635f5e2c8e674492b66688d5c2f463dc
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Linked notes

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