Oxalyl chloride → Methyl 7-tert-butylcarbonylamino-4-oxochroman-8-carboxylate

HRID 1778393Notes

Reaction equation

HRID 1778393 reaction equation
[C:1]([C:5]([NH:7][C:8]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][CH2:19][CH2:20][C:21]([OH:23])=O)[C:9]=1[C:10]([O:12][CH3:13])=[O:11])=[O:6])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O>C(Cl)Cl.CN(C=O)C>[C:1]([C:5]([NH:7][C:8]1[C:9]([C:10]([O:12][CH3:13])=[O:11])=[C:14]2[C:15]([C:21](=[O:23])[CH2:20][CH2:19][O:18]2)=[CH:16][CH:17]=1)=[O:6])([CH3:3])([CH3:4])[CH3:2]

Participants

5

Reactant 2

HCID 65578Oxalyl chlorideHCID 66686291Methyl 2-tert-butylcarbonylamino-6-(2-carboxyethoxy)-benzoate2×

Product 1

HCID 66693192Methyl 7-tert-butylcarbonylamino-4-oxochroman-8-carboxylateYield 45%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

A solution of methyl 2-tert-butylcarbonylamino-6-(2-carboxyethoxy)-benzoate (Intermediate 78, 2.73 g) in DCM (50 mL) was stirred at room temperature. DMF (5 drops) was added, followed by oxalyl chloride (2.0 g). After 30 minutes of stirring, the mixture was concentrated in vacuo and the residue was redissolved in DCM and evaporated to dryness. The residue was dissolved in DCM (50 mL) and aluminium chloride (3.38 g) was added. The resultant mixture was stirred at room temperature for 5 hours then diluted with more DCM and washed with ice/water. After separation, the aqueous phase was extracted with more DCM and the combined organic layers were washed with saturated aqueous sodium bicarbonate, dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo and the residue was purified by chromatography on silica, eluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 10-40% to give methyl 7-tert-butylcarbonylamino-4-oxochroman-8-carboxylate (1.16 g) as a white crystalline solid.

Workup

  1. concentrationthe mixture was concentrated in vacuo
  2. dissolutionthe residue was redissolved in DCM
  3. customevaporated to dryness
  4. dissolutionThe residue was dissolved in DCM (50 mL)
  5. additionaluminium chloride (3.38 g) was added
  6. stirringThe resultant mixture was stirred at room temperature for 5 hours
  7. additionthen diluted with more DCM
  8. washwashed with ice/water
  9. customAfter separation
  10. extractionthe aqueous phase was extracted with more DCM
  11. washthe combined organic layers were washed with saturated aqueous sodium bicarbonate
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationThe filtrate was concentrated in vacuo
  15. customthe residue was purified by chromatography on silica
  16. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 10-40%

Sources & evidence

ORD record
ord-9375441d21384443ad04d701d3985763
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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