Triethylamine → HCID 66822304, compound

HRID 2406568Notes

Reaction equation

HRID 2406568 reaction equation
C(Cl)(=O)C(Cl)=O.[C:7]([CH2:9][C:10]([OH:12])=O)#[N:8].[CH3:13][O:14][CH2:15][CH2:16][O:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([NH2:27])[CH2:25][CH3:26])=[CH:20][CH:19]=1.C(N(CC)CC)C>ClCCl.CN(C)C=O.O1CCCC1.ClCCl.CCOC(C)=O.O>[C:7]([CH2:9][C:10]([NH:27][CH:24]([C:21]1[CH:22]=[CH:23][C:18]([O:17][CH2:16][CH2:15][O:14][CH3:13])=[CH:19][CH:20]=1)[CH2:25][CH3:26])=[O:12])#[N:8]

Participants

10

Reactant 4

HCID 8471TriethylamineHCID 9740Cyanoacetic acidHCID 65578Oxalyl chlorideHCID 20109584HCID 20109584, compound

Product 1

HCID 66822304HCID 66822304, compoundYield 72.4%

Reagents, catalysts & solvents 5

HCID 6228DimethylformamideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

Oxalyl chloride (0.19 g, 1.49 mmol) was added to a stirred solution of cyanoacetic acid (0.107 g, 1.25 mmol) in a mixture of dichloromethane (5 mL) and 2 drops of dimethylformamide under nitrogen at ice bath temperature. After 2 hours the solution was added in one portion to a solution of 1-(4-(2-methoxyethoxy)phenyl)propan-1-amine (0.25 g, 1.2 mmol) and triethylamine (0.13 g, 1.3 mmol) in tetrahydrofuran/dichloromethane 1:1 (4 mL) at 0-5° C., and the mixture was allowed to warm slowly to room temperature. After 4 hours 80 mL of water was added and after half an hour more (30 mL) dichloromethane was added. The layers were separated and the aqueous layer extracted with additional dichloromethane. The combined extracts were washed with 1N aq sodium bicarbonate, and then sat brine, and dried over magnesium sulfate. The solvent was removed in vacuo, leaving a cloudy amber syrup which was dissolved in EtOAc/Hxa 1:1 and filtered through a short column of silica gel under pressure. The effluent was concentrated in vacuo to afford 0.24 g of the product as a cloudy pale amber syrup, sufficiently pure for the next step.

Workup

  1. additionwas added
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with additional dichloromethane
  4. washThe combined extracts were washed with 1N aq sodium bicarbonate
  5. dry with materialdried over magnesium sulfate
  6. customThe solvent was removed in vacuo
  7. customleaving a cloudy amber syrup which
  8. filtrationfiltered through a short column of silica gel under pressure
  9. concentrationThe effluent was concentrated in vacuo

Sources & evidence

ORD record
ord-0487ce87bb5146c1a59fec79bea4a890
Source dataset
uspto-grants-2014_08
Patent number
US08809377B2

Reaction notes

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