Sodium Bicarbonate → 1-(4-Chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine

HRID 1195886

Reaction equation

HRID 1195886 reaction equation
[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10](C=O)=[C:9]2[CH3:21])=[O:7])=[CH:4][CH:3]=1.[C:24]([BH3-])#[N:25].[Na+].C(=O)(O)[O-:29].[Na+]>C(O)(=O)C.C(OCC)(=O)C.C(Cl)Cl>[Cl:1][C:2]1[CH:23]=[CH:22][C:5]([C:6]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=3)[C:10]([CH2:24][NH:25][OH:29])=[C:9]2[CH3:21])=[O:7])=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 516892Sodium BicarbonateHCID 5003444Sodium cyanoborohydrideHCID 108927871-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-carboxaldehyde

Product 1

HCID 150273901-(4-Chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a suspension of 1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indole-3-carboxaldehyde, oxime (1.0 g, 2.9 mmol) in 15 ml of acetic acid is added 0.9 g (14.6 mmol) of sodium cyanoborohydride (0.9 g, 14.6 mmol). The reaction mixture is stirred vigorously for three hours whereupon an additional 0.35 g (5.6 mmol) of the reducing agent is added. After an additional 45 minutes the reaction mixture is diluted with ethyl acetate and methylene chloride, cooled to 0° C., and 300 ml of a saturated solution of sodium bicarbonate is added dropwise while continuing to stir vigorously. This mixture is diluted further with 400 ml of ethyl acetate and separated from the aqueous phase (pH=9). The organic phase is washed again with a saturated solution of sodium bicarbonate, water, and finally a saturated solution of sodium chloride. It is dried over magnesium sulfate, filtered, and concentrated to a yellow oil which is crude 1-(4-chlorobenzoyl)-N-hydroxy-5-methoxy-2-methyl-1H-indole-3-methanamine and is used without further purification in the subsequent reaction. Mass balance is quantitative. A sample recrystallized from methylene chloride has a mp of 164°.165° C. (dec).

Workup

  1. additionis added
  2. stirringto stir vigorously
  3. customseparated from the aqueous phase (pH=9)
  4. washThe organic phase is washed again with a saturated solution of sodium bicarbonate, water
  5. dry with materialIt is dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to a yellow oil which
  8. customis used without further purification in the subsequent reaction
  9. customA sample recrystallized from methylene chloride

Sources & evidence

ORD record
ord-dd9aff3321a4445a86bbc3f02c9e4a89
Source dataset
uspto-grants-1992_05
Patent number
US05112846

Linked notes

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