Triethylamine → 2-Hydroxy-N-methoxy-N-methyl-[1,1'-biphenyl]-3-carboxamide

HRID 983802Notes

Reaction equation

HRID 983802 reaction equation
[OH:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.C(Cl)(=O)C(Cl)=O.Cl.[CH3:24][NH:25][O:26][CH3:27].C(N(CC)CC)C>CCOC(C)=O.CN(C=O)C.C(Cl)Cl>[CH3:27][O:26][N:25]([CH3:24])[C:4](=[O:6])[C:3]1[CH:7]=[CH:8][CH:9]=[C:10]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:2]=1[OH:1]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 93483-Phenylsalicylic acidHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)

Product 1

HCID 110543102-Hydroxy-N-methoxy-N-methyl-[1,1'-biphenyl]-3-carboxamideYield 30.3%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-hydroxy-3-phenylbenzoic acid (218, 3.0 g, 14 mmol) is dissolved in EtOAc (50 ml) and a few drops of DMF are added. Oxalyl chloride (2.5 ml, 1.5 eq) is added and the reaction is stirred under a dry atmosphere for 1 h. The reaction mixture is then concentrated in vacuo to yield a mixture of clear oil and white solid. This mixture is diluted with CH2Cl2 (50 ml) followed by the addition of N,O-dimethyl hydroxylamine hydrochloride (1.5 g, 1.1 eq) and triethylamine (3.9 ml, 2 eq). This mixture is stirred for 12-18 h under a dry atmosphere. Dilution of the reaction mixture with EtOAc and subsequent washing with dilute HCl and brine, followed by drying (MgSO4) and concentration in vacuo yields a mixture of reaction products. Flash chromatography (20/80 EtOAc/Hexanes) afforded N-methoxy-N-methyl-2-hydroxy-3-phenylbenzamide (219, 1.09 g) as a white solid.

Workup

  1. concentrationThe reaction mixture is then concentrated in vacuo
  2. customto yield
  3. additiona mixture of clear oil and white solid
  4. stirringThis mixture is stirred for 12-18 h under a dry atmosphere
  5. washDilution of the reaction mixture with EtOAc and subsequent washing with dilute HCl and brine
  6. customby drying
  7. concentration(MgSO4) and concentration in vacuo
  8. customyields
  9. additiona mixture of reaction products

Sources & evidence

ORD record
ord-f276e7c9ffd34ec0ada420ba79622291
Source dataset
uspto-grants-2005_03
Patent number
US06867200B1

Reaction notes

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