Dimethylformamide → CI 951

HRID 2248146Notes

Reaction equation

HRID 2248146 reaction equation
[C:1](Cl)(=O)[C:2](Cl)=O.CN(C)C=O.[CH:12]([O:15][C:16]1[N:25]=[CH:24][CH:23]=[C:22]2[C:17]=1[CH:18]([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=1[C:36]([F:39])([F:38])[F:37])[C:19]([C:27]([OH:29])=[O:28])=[C:20]([CH3:26])[NH:21]2)([CH3:14])[CH3:13]>O1CCOCC1>[CH2:1]([O:28][C:27]([C:19]1[CH:18]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][C:31]=2[C:36]([F:38])([F:39])[F:37])[C:17]2[C:22](=[CH:23][CH:24]=[N:25][C:16]=2[O:15][CH:12]([CH3:14])[CH3:13])[NH:21][C:20]=1[CH3:26])=[O:29])[CH3:2]

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 13670941(+)-1,4-Dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid

Product 1

HCID 128276CI 951

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
3 °C

Procedure

31.4 mg oxalyl chloride are added to a solution of 0.5 mL anhydrous dimethylformamide in 3 mL anhydrous dioxan cooled to 3° C., followed by stirring for 40 minutes at 0° to 5° C. After adding 85 mg (+)-1,4-dihydro-5-isopropoxy-2-methyl-4-(2-trifluoromethylphenyl)-1,6-naphthyridine-3-carboxylic acid, dissolved in 1 mL anhydrous dioxan, the cooling is removed, followed by stirring for 2.5 hours. After adding 2 mL ethanol, the reaction mixture is first stirred for 2 hours at ambient temperature and thereafter for 30 minutes at 40° to 50° C. The reaction mixture is subsequently stirred with 30 mL 2N aqueous sodium carbonate solution and 10 mL dichloromethane. The organic phase is separated off and the aqueous phase subsequently extracted three times with 10 mL amounts of dichloromethane. The combined organic phases are dried over anhydrous sodium sulfate and then evaporated to dryness. The residue is purified over silica gel with n-hexane/ethyl acetate (1:1 v/v) as elution agent and subsequently recrystallized from n-hexane. Yield: 32 mg (38.5% of theory); mp 130° C.; [α]D =+105° (c=0.5/dichloromethane).

Workup

  1. customthe cooling is removed
  2. stirringby stirring for 2.5 hours
  3. additionAfter adding 2 mL ethanol
  4. stirringthe reaction mixture is first stirred for 2 hours at ambient temperature
  5. waitfor 30 minutes at 40° to 50° C
  6. stirringThe reaction mixture is subsequently stirred with 30 mL 2N aqueous sodium carbonate solution and 10 mL dichloromethane
  7. customThe organic phase is separated off
  8. extractionthe aqueous phase subsequently extracted three times with 10 mL amounts of dichloromethane
  9. dry with materialThe combined organic phases are dried over anhydrous sodium sulfate
  10. customevaporated to dryness
  11. customThe residue is purified over silica gel with n-hexane/ethyl acetate (1:1 v/v) as elution agent
  12. customsubsequently recrystallized from n-hexane
  13. custom[α]D =+105° (c=0.5/dichloromethane)

Sources & evidence

ORD record
ord-c0fd989177a14a2a8378effedec861a0
Source dataset
uspto-grants-1991_08
Patent number
US05037987

Reaction notes

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