Chlorine → HCID 58934814, compound

HRID 855111Notes

Reaction equation

HRID 855111 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]2[C:4]=1[CH:5]=[C:6]([C:19]([OH:21])=[O:20])[CH:7]([C:15]([F:18])([F:17])[F:16])[O:8]2.[Cl:22]Cl>C(O)(=O)C.[Zn]>[Cl:22][C:12]1[C:3]([O:2][CH3:1])=[C:4]2[C:9](=[CH:10][C:11]=1[O:13][CH3:14])[O:8][CH:7]([C:15]([F:16])([F:17])[F:18])[C:6]([C:19]([OH:21])=[O:20])=[CH:5]2

Participants

5

Reactant 2

HCID 24526Chlorine2×HCID 18337485HCID 18337485, compound

Product 1

HCID 58934814HCID 58934814, compoundYield 17.2%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalystHCID 176Acetic AcidSolvent2×

Procedure

The solution of the 5,7-dimethoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid from Example 34 (WO 00/23433) (150 mg, 0.49 mmole) in acetic acid (1.0 mL) was stirred at 10° C. The pre-prepared solution of Cl2 (gas) in acetic acid (1.1 mL, 0.64 mmol) was added to above solution. The mixture was stirred for 2 hours. After Cl2 (gas) was blown away, Zn powder (5 eq) was added to the mixture and the mixture was stirred for 30 min. Zn salts were removed by filtration and the filtrate was evaporated to dryness. The residue was purified by RPHPLC and eluted with 30 to 85% ACN in water with 0.05% TFA. The Ist peak fractions were combined to give the desired compound 28.6 mg (17.2%) as mono-chloro compound: LCMS m/z 339.05 (M+H) at 5.474 min. ESHRMS m/z 337.0112 (M−H, C13H9O5F3Cl, Calc'd 337.0085). 1H NMR (CDCl3/400 MHz) 7.90 (s, 1H), 6.67 (s, 1H), 5.82 (q, 1H, J=6.8 Hz), 3.97 (s, 3H), 3.94 (s, 3H).

Workup

  1. stirringthe mixture was stirred for 30 min
  2. customZn salts were removed by filtration
  3. customthe filtrate was evaporated to dryness
  4. customThe residue was purified by RPHPLC
  5. washeluted with 30 to 85% ACN in water with 0.05% TFA

Sources & evidence

ORD record
ord-e79731e810e445189af419e1875408f0
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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