Methanol → 4-(2-Carbazol-9-yl-ethyl)-N-hydroxy-benzamide

HRID 1970826Notes

Reaction equation

HRID 1970826 reaction equation
C[O:2][C:3](=O)[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH2:11][N:12]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:18]3[C:13]2=[CH:14][CH:15]=[CH:16][CH:17]=3)=[CH:6][CH:5]=1.Cl.[NH2:27][OH:28].C[O-].[Na+].CO>CN(C=O)C.C(OCC)(=O)C.C(=O)(O)[O-].[Na+]>[CH:23]1[C:24]2[N:12]([CH2:11][CH2:10][C:7]3[CH:8]=[CH:9][C:4]([C:3]([NH:27][OH:28])=[O:2])=[CH:5][CH:6]=3)[C:13]3[C:18](=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:19]=2[CH:20]=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 443297Hydroxyamine hydrochlorideHCID 10942334Sodium MethoxideHCID 668730964-(2-Carbazol-9-yl-ethyl)benzoic acid methyl ester

Product 1

HCID 508989484-(2-Carbazol-9-yl-ethyl)-N-hydroxy-benzamideYield 7%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

4-(2-Carbazol-9-ylethyl)benzoic acid methyl ester (27) (0.15 g, 0.46 mmol) and hydroxylamine hydrochloride (0.19 g, 2.7 mmol) were placed under argon and dissolved in DMF (3 mL). To this was added a 25% sodium methoxide solution in methanol (0.79 g, 3.6 mmol) which resulted in immediate precipitation of a white solid. The reaction was stirred for 24 h at room temperature after which it was taken up in 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 (10 mg, 7%) as an off-white solid. 1H NMR (400 MHz, DMSO): δ 11.14 (br, 1H), 8.14 (d, 2H, J=7.8 Hz), 7.62 (m, 4H), 7.40 (m, 4H), 7.18 (t, 2H, J=7.6 Hz), 4.62 (t, 2H, J=7.0 Hz), 3.11 (t, 2H, J=7.6 Hz). 13C NMR (100 MHz, DMSO): δ 140.2, 129.4, 127.3, 126.1, 122.5, 120.7, 119.2, 109.7, 44.1, 34.7. ESI-HRMS (m/z): [M−H]− calcd. for C21H18N2O2, 329.1298. found, 329.1273. Analytical HPLC: Purity=100%, tR=9.13 min, Method B.

Workup

  1. customresulted in immediate precipitation of a white solid
  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-aadd3ec8d823441aaff20524a953d8df
Source dataset
uspto-grants-2013_04
Patent number
US08431538B2

Reaction notes

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