Potassium Carbonate → Ethyl 7-(4-(tert-butoxycarbonyl)-2-nitrophenoxy)-6,8-dichlorochroman-4-carboxylate

HRID 1626369Notes

Reaction equation

HRID 1626369 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[C:10]([Cl:13])[C:11]=1[OH:12])[O:8][CH2:7][CH2:6][CH:5]2[C:14]([O:16][CH2:17][CH3:18])=[O:15].F[C:20]1[CH:32]=[CH:31][C:23]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])=[CH:22][C:21]=1[N+:33]([O-:35])=[O:34].C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1>[C:27]([O:26][C:24]([C:23]1[CH:31]=[CH:32][C:20]([O:12][C:11]2[C:10]([Cl:13])=[C:9]3[C:4]([CH:5]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH2:6][CH2:7][O:8]3)=[CH:3][C:2]=2[Cl:1])=[C:21]([N+:33]([O-:35])=[O:34])[CH:22]=1)=[O:25])([CH3:30])([CH3:28])[CH3:29]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 58748597tert-Butyl 4-fluoro-3-nitrobenzoateHCID 67080489Ethyl 6,8-dichloro-7-hydroxychroman-4-carboxylate

Product 1

HCID 67080485Ethyl 7-(4-(tert-butoxycarbonyl)-2-nitrophenoxy)-6,8-dichlorochroman-4-carboxylateYield 62.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of ethyl 6,8-dichloro-7-hydroxychroman-4-carboxylate (2.50 g, 8.59 mmol), tert-butyl 4-fluoro-3-nitrobenzoate (2.20 g, 9.12 mmol) and potassium carbonate (1.8 g, 13 mmol) in 50 mL of NMP was degassed with argon for 10 minutes and was heated at 80° C. overnight. After stirring overnight the reaction mixture was cooled to ambient temperature and diluted with 600 mL of water. The pH was adjusted to 1-2 with 1 N HCl and the resulting solids were collected by filtration. The solids were dissolved in ethyl acetate and the solution was washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash column chromatography, eluting with 20% ethyl acetate in hexanes to give ethyl 7-(4-(tert-butoxycarbonyl)-2-nitrophenoxy)-6,8-dichlorochroman-4-carboxylate (2.74 g, 62.3% yield) as an oil.

Workup

  1. customwas degassed with argon for 10 minutes
  2. temperaturewas cooled to ambient temperature
  3. additiondiluted with 600 mL of water
  4. filtrationthe resulting solids were collected by filtration
  5. dissolutionThe solids were dissolved in ethyl acetate
  6. washthe solution was washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by flash column chromatography
  11. washeluting with 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ce80023f5d404dddb9c5819a7faac399
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

Loading…