Acetic Acid → ethyl 7-tert-butyl-6-chloro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 2214840Notes

Reaction equation

HRID 2214840 reaction equation
[CH3:1][C:2]([C:5]1[CH:23]=[CH:22][C:8]2[CH:9]=[C:10]([C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH:11]([C:13]([F:16])([F:15])[F:14])[O:12][C:7]=2[CH:6]=1)([CH3:4])[CH3:3].C(O)(=O)C.O.[Cl:29]Cl>C(OCC)(=O)C.[Zn]>[Cl:29][C:23]1[C:5]([C:2]([CH3:3])([CH3:1])[CH3:4])=[CH:6][C:7]2[O:12][CH:11]([C:13]([F:15])([F:16])[F:14])[C:10]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:9][C:8]=2[CH:22]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 24526ChlorineHCID 21883685Ethyl 7-(1,1-dimethylethyl)-2-(trifluoromethyl)-2h-1-benzopyran-3-carboxylate

Product 1

HCID 21883510ethyl 7-tert-butyl-6-chloro-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 106.6%

Reagents, catalysts & solvents 2

HCID 23994ZincCatalyst2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
15 °C

Procedure

A one liter three-neck flask equipped with mechanical stirrer and gas inlet tube was charged with the ester (Step 2) (100 g, 0.3 mole) and acetic acid (300 mL). While cooling (water bath) the reaction mixture, chlorine gas (37.6 g, 0.53 mole) was added which caused the temperature to rise to 48° C. After stirring for two hours, the reaction was cooled in an ice-water bath to 15° C. Zinc powder (19.5 g, 0.3 mole) was added in one portion which caused the temperature to rise to 72° C. After cooling to room temperature additional zinc powder (5.0 g, 0.08 mole) was added and the mixture was stirred for 0.5 hour longer. The crude mixture was filtered through diatomaceous earth and was concentrated in vacuo yielding an oil. The oil was dissolved in ethyl acetate (700 mL) washed with brine-water (1:1, 1 L) and brine (0.5 L). The resulting aqueous phase was extracted with ethyl acetate (700 mL). This ethyl acetate phase was washed with brine-water (1:1, 1 L) and brine (0.5 L). The combined organic phases were dried over MgSO4, filtered and concentrated in vacuo yielding the title compound as a yellow oil (116 g, 106%). This material, which contained some entrained ethyl acetate, was of suitable purity to be used in subsequent steps without further purification.

Workup

  1. customA one liter three-neck flask equipped with mechanical stirrer and gas inlet tube
  2. additionwas added which
  3. customto rise to 48° C
  4. customto rise to 72° C
  5. additionwas added
  6. stirringthe mixture was stirred for 0.5 hour longer
  7. filtrationThe crude mixture was filtered through diatomaceous earth
  8. concentrationwas concentrated in vacuo
  9. customyielding an oil
  10. washwashed with brine-water (1:1, 1 L) and brine (0.5 L)
  11. extractionThe resulting aqueous phase was extracted with ethyl acetate (700 mL)
  12. washThis ethyl acetate phase was washed with brine-water (1:1, 1 L) and brine (0.5 L)
  13. dry with materialThe combined organic phases were dried over MgSO4
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9276532165b54226b0c1e91f2b1be07c
Source dataset
uspto-grants-2006_09
Patent number
US07109211B2

Reaction notes

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