Indole-3-Butyric Acid → N-Methyl-N-Methoxy-4-(3-indolyl)butyramide

HRID 883

Reaction equation

HRID 883 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O)=[CH:2]1.[CH:16](N(CC)C(C)C)(C)C.Cl.[CH3:26][N:27](C)[OH:28].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(#N)C>[CH3:26][N:27]([O:28][CH3:16])[C:13](=[O:15])[CH2:12][CH2:11][CH2:10][C:3]1[C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[NH:1][CH:2]=1

Participants

6

Reactant 4

HCID 8617Indole-3-Butyric AcidHCID 27969N,N-dimethylhydroxylamine hydrochlorideHCID 81531DiisopropylethylamineHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate

Product 1

HCID 11107631N-Methyl-N-Methoxy-4-(3-indolyl)butyramideYield 94.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a slurry of 1.75 g (8.61 mmol) of 3-indolebutyric acid (Aldrich Chemical Co.) in acetonitrile at room temperature was added 7.0 mL (40.2 mmol) of N,N-diisopropylethylamine, 1.0 g (10.3 mmol) of N,N-dimethylhydroxylamine hydrochloride and 4.19 g (9.5 mmol) of benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate (BOP reagent) and the resulting mixture was allowed to stir at room temperature overnight and was then concentrated to dryness. The residue was dissolved into ethyl acetate and washed with water, 0.5N HCl, saturated NaHCO3 and brine and then dried over MgSO4 and concentrated. Flash chromatography (elution with a gradient of 2-10% ether in methylene chloride) provided 2.0 g of the amide 139. 1H NMR consistent with structure.

Workup

  1. concentrationwas then concentrated to dryness
  2. dissolutionThe residue was dissolved into ethyl acetate
  3. washwashed with water, 0.5N HCl, saturated NaHCO3 and brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. washFlash chromatography (elution with a gradient of 2-10% ether in methylene chloride)

Sources & evidence

ORD record
ord-5ab94114d8b645e082906ef9a74075cf
Source dataset
uspto-grants-1998_03
Patent number
US05723459

Linked notes

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