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

HRID 1048050Notes

Reaction equation

HRID 1048050 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+]>CN1CCCC1=O>[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 104.1%

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 (35 g, 120.22 mmol), tert-butyl 4-fluoro-3-nitrobenzoate (31.1 g, 128.93 mmol), K2CO3 (24.923 g, 180.33 mmol), and 1-methyl-2-pyrrolidinone (500 mL) was purged with Argon (bubbled through) for 15 minutes. The mixture was heated to 80° C. for 4 hours under Argon atmosphere. The mixture was cooled to ambient temperature and poured into 3 liters of water. The pH was adjusted to pH 2 by addition of concentrated HCl (4×10 ml). A solid precipitated out as HCl was added and gas evolution was observed. The crude mixture was filtered and the solid was dissolved in EtOAc (1 liter). The EtOAc solution was washed with 2N HCl solution (200 ml), water (2×200 ml), and brine (200 ml), dried over MgSO4, filtered, and concentrated to provide 64.1 g of the title compound as a dark solid (104%).

Workup

  1. customwas purged with Argon (bubbled through) for 15 minutes
  2. temperatureThe mixture was cooled to ambient temperature
  3. additionpoured into 3 liters of water
  4. additionThe pH was adjusted to pH 2 by addition of concentrated HCl (4×10 ml)
  5. customA solid precipitated out as HCl
  6. additionwas added
  7. filtrationThe crude mixture was filtered
  8. dissolutionthe solid was dissolved in EtOAc (1 liter)
  9. washThe EtOAc solution was washed with 2N HCl solution (200 ml), water (2×200 ml), and brine (200 ml)
  10. dry with materialdried over MgSO4
  11. filtrationfiltered
  12. concentrationconcentrated

Sources & evidence

ORD record
ord-f0afe3f27252471b89865a93d0d3d9c9
Source dataset
uspto-grants-2013_10
Patent number
US08569522B2

Reaction notes

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