Dimethylformamide → HCID 67042187, compound

HRID 62741Notes

Reaction equation

HRID 62741 reaction equation
[CH2:1]([O:8][C:9]1[C:17](OC2CCCCC2)=[CH:16][C:12]([C:13]([OH:15])=O)=[CH:11][C:10]=1[Cl:25])[C:2]1C=CC=CC=1.C(Cl)(=O)C([Cl:29])=O.CN(C=O)C.[NH2:37][C:38]1[CH:50]=[CH:49][C:41]([C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])=[C:40]([O:51][CH3:52])[CH:39]=1>C(Cl)Cl>[Cl:29][C:17]1[CH:16]=[C:12]([CH:11]=[C:10]([Cl:25])[C:9]=1[O:8][CH2:1][CH3:2])[C:13]([NH:37][C:38]1[CH:50]=[CH:49][C:41]([C:42]([O:44][C:45]([CH3:47])([CH3:48])[CH3:46])=[O:43])=[C:40]([O:51][CH3:52])[CH:39]=1)=[O:15]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 593777671215074-48-8HCID 67041687HCID 67041687, compound

Product 1

HCID 67042187HCID 67042187, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3,5-Dichloro-4-ethoxybenzoic acid (4) (75 mg, 0.32 mmol) in DCM (5 mL) was treated with oxalyl chloride (56 μL, 0.64 mmol) dropwise, followed by a drop of DMF. The reaction mixture was stirred at RT for 1 h, and then the solvent was removed in vacuo. The residue was dissolved in DCM (5 mL) and TEA (133 μL, 957 μmol) was added. The mixture was added to tert-butyl 4-amino-2-methoxybenzoate (3) (71 mg, 0.32 mmol) and stirred at RT for 16 h. The mixture was sequentially washed with sat. aq. NaHCO3 (5 mL) and 1 M HCl (5 mL), and the organic phase was concentrated in vacuo. The residue was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane) to afford tert-butyl 4-(3,5-dichloro-4-ethoxybenzamido)-2-methoxybenzoate (5) (59 mg, 42%) as a white solid: m/z 384 [M−tBu+2H]+ (ES+); 1H-NMR (400 MHz, DMSO-d6) δ: 10.51 (1H, s), 8.09 (2H, s), 7.63 (1H, d), 7.60 (1H, d), 7.43 (1H, dd), 4.15 (2H, q), 3.81 (3H, s), 1.51 (9H, s), 1.41 (3H, t).

Workup

  1. customthe solvent was removed in vacuo
  2. dissolutionThe residue was dissolved in DCM (5 mL)
  3. stirringstirred at RT for 16 h
  4. washThe mixture was sequentially washed with sat. aq. NaHCO3 (5 mL) and 1 M HCl (5 mL)
  5. concentrationthe organic phase was concentrated in vacuo
  6. customThe residue was purified by silica gel chromatography (12 g, 0-100% EtOAc in isohexane)

Sources & evidence

ORD record
ord-6e19ce8fcc1b4c54a5534802ac1e02fe
Source dataset
uspto-grants-2016_09
Patent number
US09447028B2

Reaction notes

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