Dimethylformamide → methyl 7-tert-butylcarbonylamino-4-chloro-3-formyl-2H-chromene-8-carboxylate

HRID 1778392Notes

Reaction equation

HRID 1778392 reaction equation
[C:1]([C:5]([NH:7][C:8]1[C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]2[C:11]([C:12](=O)[CH2:13][CH2:14][O:15]2)=[CH:10][CH:9]=1)=[O:6])([CH3:4])([CH3:3])[CH3:2].CN([CH:26]=[O:27])C.P(Cl)(Cl)([Cl:30])=O>ClC=C(Cl)Cl.C(Cl)Cl>[C:1]([C:5]([NH:7][C:8]1[C:17]([C:18]([O:20][CH3:21])=[O:19])=[C:16]2[C:11]([C:12]([Cl:30])=[C:13]([CH:26]=[O:27])[CH2:14][O:15]2)=[CH:10][CH:9]=1)=[O:6])([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 6228DimethylformamideHCID 24813Phosphorus oxychloride2×HCID 66693192Methyl 7-tert-butylcarbonylamino-4-oxochroman-8-carboxylate2×

Product 1

HCID 86684737methyl 7-tert-butylcarbonylamino-4-chloro-3-formyl-2H-chromene-8-carboxylate

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 6575TrichloroethyleneSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of methyl 7-tert-butylcarbonylamino-4-oxochroman-8-carboxylate (Intermediate 77, 1.32 g) in trichloroethylene (25 mL) was treated with DMF (1.5 mL), followed by dropwise addition of phosphorus oxychloride (0.998 g). The resultant mixture was heated at 60° C. for 2 hours. A further amount of phosphorus oxychloride (0.200 g) was added and the mixture was heated at 60° C. for 40 minutes. After cooling, the mixture was diluted with DCM and washed with saturated aqueous sodium bicarbonate solution. The aqueous phase was extracted with DCM and the combined organic layers were washed with brine, 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 0-25% to give methyl 7-tert-butylcarbonylamino-4-chloro-3-formyl-2H-chromene-8-carboxylate (1.175 g) as a yellow solid.

Workup

  1. temperatureAfter cooling
  2. washwashed with saturated aqueous sodium bicarbonate solution
  3. extractionThe aqueous phase was extracted with DCM
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated in vacuo
  8. customthe residue was purified by chromatography on silica
  9. washeluting with a mixture of ethyl acetate and cyclohexane, with a gradient of 0-25%

Sources & evidence

ORD record
ord-e078fc4cc76940f58b34499b6204e383
Source dataset
uspto-grants-2016_02
Patent number
US09266896B2

Reaction notes

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