Cyanoacetic acid → HCID 66822001, compound

HRID 2406558Notes

Reaction equation

HRID 2406558 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][O:16][C:17]1[CH:22]=[CH:21][C:20]([CH:23]([NH2:27])[CH2:24][CH2:25][CH3:26])=[CH:19][CH:18]=1.C(=O)(O)[O-].[Na+]>O1CCCC1.CN(C=O)C>[C:7]([CH2:9][C:10]([NH:27][CH:23]([C:20]1[CH:19]=[CH:18][C:17]([O:16][CH2:15][O:14][CH3:13])=[CH:22][CH:21]=1)[CH2:24][CH2:25][CH3:26])=[O:12])#[N:8]

Participants

7

Reactant 4

HCID 9740Cyanoacetic acidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 66822056HCID 66822056, compound

Product 1

HCID 66822001HCID 66822001, compoundYield 102.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Oxalyl chloride (1.03 g, 8.15 mmol) was added drop-wise at ice bath temperature under nitrogen to a stirred solution of cyanoacetic acid (0.67 g, 7.9 mmol) in tetrahydrofuran (15 mL) to which 1-2 drops of DMF had been added. The mixture was stirred for an hour, then added slowly in one portion to a stirred solution of 1-(4-(methoxymethoxy)phenyl)butan-1-amine (1.1 g, 5.3 mmol) in THF (15 mL) at ice bath temperature under nitrogen. The mixture was allowed to warm gradually to room temperature and after 20 hours was stirred into 50 mL of saturated aq sodium bicarbonate and extracted 3× with dichloromethane. The combined extracts were washed with saturated brine, dried over magnesium sulfate, and concentrated in vacuo, leaving 1.5 g of dark violet syrup. The product was flash chromatographed on a column (50×70 mm) of silica gel (43-60 μm) eluting with Hxa/EtOAc 1:1 to afford 1.0 g (69%) of clear, dark oil; homogeneous by TLC.

Workup

  1. additionhad been added
  2. extractionextracted 3× with dichloromethane
  3. washThe combined extracts were washed with saturated brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0f84c260eacb4e89883e92d648304d93
Source dataset
uspto-grants-2014_08
Patent number
US08809377B2

Reaction notes

Loading…