Water → Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylate

HRID 1626371Notes

Reaction equation

HRID 1626371 reaction equation
N[C:2]1[CH:25]=[C:24]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH:23]=[CH:22][C:3]=1[O:4][C:5]1[C:14]([Cl:15])=[C:13]2[C:8]([CH:9]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:11][O:12]2)=[CH:7][C:6]=1[Cl:21].N(OCC(C)C)=O.O>CN(C=O)C>[C:29]([O:28][C:26]([C:24]1[CH:25]=[CH:2][C:3]([O:4][C:5]2[C:14]([Cl:15])=[C:13]3[C:8]([CH:9]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10][CH2:11][O:12]3)=[CH:7][C:6]=2[Cl:21])=[CH:22][CH:23]=1)=[O:27])([CH3:30])([CH3:31])[CH3:32]

Participants

5

Reactant 3

HCID 962WaterHCID 10958Isobutyl nitriteHCID 67080422Ethyl 7-(2-amino-4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylate

Product 1

HCID 67080347Ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylateYield 90.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 7-(2-amino-4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylate (2.1 g, 4.4 mmol) in 20 mL of DMF at 70° C. was added isobutyl nitrite (1.29 mL, 10.9 mmol) dropwise over ten minutes. After an additional 15 minutes the reaction was cooled to ambient temperature and poured into 600 mL of water. The product was extracted with ethyl acetate and the combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated. The crude product was dissolved in dichloromethane, concentrated onto silica gel and purified by flash column chromatography, eluting with 20% ethyl acetate in hexanes to give ethyl 7-(4-(tert-butoxycarbonyl)phenoxy)-6,8-dichlorochroman-4-carboxylate (1.85 g, 90.9% yield) as a foam.

Workup

  1. extractionThe product was extracted with ethyl acetate
  2. washthe combined organics were washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. dissolutionThe crude product was dissolved in dichloromethane
  7. concentrationconcentrated onto silica gel
  8. custompurified by flash column chromatography
  9. washeluting with 20% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-b83f87cd56f74f88a8f9196f268bc1ab
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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