3,5-Dihydroxybenzoic Acid → 3,5-Dihydroxybenzamide

HRID 598811

Reaction equation

HRID 598811 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([OH:11])[CH:10]=1)[C:5](O)=[O:6].Cl.C[N:14](C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.CCN(CC)CC>C(Cl)Cl.CCOC(C)=O.CN(C=O)C>[OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([OH:11])[CH:10]=1)[C:5]([NH2:14])=[O:6]

Participants

8

Reactant 4

HCID 74243,5-Dihydroxybenzoic AcidHCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrate

Product 1

HCID 766043,5-Dihydroxybenzamide

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

After reaction step (a), the resulting amine (1 equiv.), 3,5-dihydroxybenzoic acid (1 equiv.), EDCI (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride) (1.2 equiv.), HOBt (1-hydroxybenzotriazole hydrate) (1.2 equiv.), and Et3N (4 equiv.) in CH2Cl2.DMF (9:1) were stirred for 12 hours at room temperature. Then the reaction mixture was diluted with EtOAc and the organic layer washed with brine. The combined organic layer was dried over anhydrous Na2SO4 and concentrated. Purification of the resulting crude product by flash silica gel chromatography provided corresponding 3,5-dihydroxybenzamide derivative. The above derivative (1 equiv.) and active carbonate 4 (1.1 equiv.) in THF were stirred under hydrogen atmosphere in presence of Pd—C (10%) for 12 hours at room temperature. Then the reaction mixture was filtered and the organic layer washed with brine. The combined organic layer was dried over anhydrous Na2SO4 and concentrated. Purification of the resulting crude product by flash silica gel chromatography provided compound 134 as a solid.

Workup

  1. customAfter reaction step (a)
  2. washthe organic layer washed with brine
  3. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  4. concentrationconcentrated
  5. customPurification of the resulting crude product by flash silica gel chromatography

Sources & evidence

ORD record
ord-7efcf994c2e943c1970d84ab2f92882f
Source dataset
uspto-grants-2011_03
Patent number
US07897635B2

Linked notes

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