Hydroxyamine hydrochloride → 4-Carbazol-9-ylmethyl-N-hydroxybenzamide

HRID 403633Notes

Reaction equation

HRID 403633 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][N:11]2[C:23]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:17]3[C:12]2=[CH:13][CH:14]=[CH:15][CH:16]=3)=[CH:6][CH:5]=1.Cl.[NH2:26][OH:27].C[O-].[Na+]>CO.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH:22]1[C:23]2[N:11]([CH2:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([NH:26][OH:27])=[O:2])=[CH:5][CH:6]=3)[C:12]3[C:17](=[CH:16][CH:15]=[CH:14][CH:13]=3)[C:18]=2[CH:19]=[CH:20][CH:21]=1

Participants

7

Reactant 3

HCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 668730724-Carbazol-9-ylmethylbenzoic acid methyl ester

Product 1

HCID 469188244-Carbazol-9-ylmethyl-N-hydroxybenzamideYield 41%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

4-Carbazol-9-ylmethylbenzoic acid methyl ester (19) (1.0 g, 3.2 mmol) and hydroxylamine hydrochloride (1.3 g, 19.0 mmol) were placed under argon and dissolved in 5 mL of methanol. To it was added a 25% sodium methoxide solution in methanol (5.48 g, 25.4 mmol) which resulted in the formation of a white precipitate. The reaction was stirred for 24 h at room temperature after which the reaction was diluted with 20 mL ethyl acetate and 20 mL of saturated sodium bicarbonate. The organic layer was isolated and the aqueous layer was further extracted with ethyl acetate (2×10 mL). The combined organic layers were washed with brine (10 mL), dried (Na2SO4) and concentrated in vacuo. The crude extract was purified by HPLC to yield the title compound (0.41 g, 41%) as an off-white solid. 1H NMR (400 MHz, DMSO): δ 11.09 (s, 1H), 8.97 (s, 1H), 8.18 (d, 2H, J=7.8 Hz), 7.61 (m, 4H), 7.43 (t, 2H, J=8.0 Hz), 7.19 (m, 4H), 5.71 (s, 2H). 13C NMR (100 MHz, DMSO): δ 164.0, 140.2, 141.1, 132.0, 127.3, 126.8, 126.0, 122.3, 120.5, 119.2, 109.5, 45.4. ESI-HRMS (m/z): [M+H]+ calcd. for C21H17NO2, 317.1149. found, 317.1143. Analytical HPLC: Purity=99%, tR=10.69 min, Method A.

Workup

  1. customresulted in the formation of a white precipitate
  2. customThe organic layer was isolated
  3. extractionthe aqueous layer was further extracted with ethyl acetate (2×10 mL)
  4. washThe combined organic layers were washed with brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo
  7. extractionThe crude extract
  8. customwas purified by HPLC

Sources & evidence

ORD record
ord-8dfa79801eda45d3ad71ab1778820a0e
Source dataset
uspto-grants-2014_06
Patent number
US08748451B2

Reaction notes

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