Triethylamine → Tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoate

HRID 1820989Notes

Reaction equation

HRID 1820989 reaction equation
[Cl:1][C:2]1[C:3]([Cl:11])=[N:4][CH:5]=[C:6]([CH:10]=1)[C:7]([OH:9])=O.C(Cl)(=O)C(Cl)=O.[CH3:18][C:19]1[CH:20]=[C:21]([CH:27]=[CH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH:22]=[CH:23][C:24]=1[C:25]#[N:26].C([N:38](CC)CC)C>C(Cl)Cl.CN(C=O)C.ClC(Cl)C>[Cl:1][C:2]1[CH:10]=[C:6]([C:7]2[O:9][N:38]=[C:25]([C:24]3[CH:23]=[CH:22][C:21]([CH2:27][CH2:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:20][C:19]=3[CH3:18])[N:26]=2)[CH:5]=[N:4][C:3]=1[Cl:11]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 2479875,6-Dichloronicotinic acidHCID 68649265Tert-butyl 3-(4-cyano-3-methylphenyl)acrylate

Product 1

HCID 86623617Tert-butyl 3-(4-(5-(5,6-dichloropyridin-3-yl)-1,2,4-oxadiazol-3-yl)-3-methylphenyl)propanoateYield 80.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Procedure

To a solution of 200 mg (1.04 mmol) of 5,6-dichloronicotinic acid in 5.0 mL of CH2Cl2 was added 273 μL (3.13 mmol) of oxalyl chloride and one drop of DMF. After stirring at rt overnight, the mixture was concentrated and dried azeotropically using toluene (3×5 mL). The residue was dissolved in 5.0 mL of dichloroethane and added to a solution of 242 mg (0.87 mmol) of N-HYDROXYAMIDINE 1 and 182 μL (1.30 mmol) of triethylamine in 5.0 mL of dichloroethane. After stirring at rt for 1 hr and at 120° C. overnight, the reaction mixture was cooled to rt and concentrated. Chromatography on a Biotage 40S cartridge using 1:19 v/v EtOAc/hexanes as the eluant gave 303 mg of the title compound: 1H NMR (500 MHz, CDCl3) δ 1.44 (s, 9H), 2.58 (t, J=7.8, 2H), 2.65 (s, 3H), 2.95 (t, J=7.7, 2H), 7.17-7.19 (m, 2H), 8.00 (d, J=8.5, 1H), 8.53 (d, J=2.0, 1H), 9.08 (d, J=2.0, 1H).

Workup

  1. concentrationthe mixture was concentrated
  2. dry with materialdried azeotropically using toluene (3×5 mL)
  3. dissolutionThe residue was dissolved in 5.0 mL of dichloroethane
  4. stirringAfter stirring at rt for 1 hr and at 120° C. overnight
  5. temperaturethe reaction mixture was cooled to rt
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-91f3c7e23d79423ca89a6797e53c444c
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

Loading…