Oxalyl chloride → HCID 68853800, compound

HRID 1821003Notes

Reaction equation

HRID 1821003 reaction equation
[C:1]([C:3]1[C:4]([O:12][CH:13]([CH3:15])[CH3:14])=[C:5]([CH:9]=[CH:10][CH:11]=1)C(O)=O)#[N:2].C(Cl)(=O)[C:17](Cl)=[O:18].[Br:22][C:23]1[CH:32]=[CH:31][C:26]([C:27]([NH:29][NH2:30])=[O:28])=[C:25]([CH3:33])[CH:24]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[C:1]([C:3]1[CH:11]=[C:10]([C:17]([NH:30][NH:29][C:27](=[O:28])[C:26]2[CH:31]=[CH:32][C:23]([Br:22])=[CH:24][C:25]=2[CH3:33])=[O:18])[CH:9]=[CH:5][C:4]=1[O:12][CH:13]([CH3:14])[CH3:15])#[N:2]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 43629611HCID 43629611, compoundHCID 69062573HCID 69062573, compound

Product 1

HCID 68853800HCID 68853800, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 170 mg (0.83 mmol) of 3-cyanoisopropyloxybenzoic acid in 10 mL of anhydrous CH2Cl2 and 10 μL of DMF was treated with 1.0 mL of oxalyl chloride. The reaction mixture was heated to 50° C. for 10 minutes, cooled to rt and the solvents were removed under reduced pressure. The resulting crude material was dissolved in 10 mL of EtOAc and added in one portion to a vigorously stirring biphasic mixture of 209 mg of 4-bromo-2-methylbenzhydrazide (0.91 mmol), 20 mL of EtOAc, and 20 mL of saturated aqueous solution of sodium bicarbonate. After 30 minutes, the precipitate was collected by filtration and rinsed with 2×10 mL of water and dried in a desiccator overnight. Product (299 mg) was found to be >95% pure by 1H NMR and used in subsequent cyclization step without further purification: 1H NMR (500 MHZ, temp.=50° C., CDCl3) δ 1.55 (d, J=6.5, 6H), 2.51 (s, 3H), 4.78 (sep, J=6.5, 1H), 7.04 (d, J=9.0, 1H), 7.42 (s, 2H), 7.48 (s, 1H), 8.02 (dd, J=9.0, 2.0, 1H), 8.10 (d, J=2.0, 1H), 8.66 (d, J=2.0, 1H), 9.18 (d, J=2.0, 1H).

Workup

  1. temperaturecooled to rt
  2. customthe solvents were removed under reduced pressure
  3. dissolutionThe resulting crude material was dissolved in 10 mL of EtOAc
  4. additionadded in one portion to
  5. filtrationthe precipitate was collected by filtration
  6. washrinsed with 2×10 mL of water
  7. customdried in a desiccator overnight
  8. customused in subsequent cyclization step without further purification

Sources & evidence

ORD record
ord-b808e710ebc54d6eb6e1ab261a36af7b
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

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