Water → 4-((2-(4-fluorophenyl)-3-(3,4,5-trimethoxyphenyl)acrylamido)methyl)-N-hydroxybenzamide

HRID 444725Notes

Reaction equation

HRID 444725 reaction equation
Cl.[NH2:2][OH:3].[OH-].[K+].[F:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[CH:29][C:30]2[CH:35]=[C:34]([O:36][CH3:37])[C:33]([O:38][CH3:39])=[C:32]([O:40][CH3:41])[CH:31]=2)[C:14]([NH:16][CH2:17][C:18]2[CH:28]=[CH:27][C:21]([C:22](OCC)=[O:23])=[CH:20][CH:19]=2)=[O:15])=[CH:9][CH:8]=1.O>CO.C(O)(=O)C>[F:6][C:7]1[CH:8]=[CH:9][C:10]([C:13](=[CH:29][C:30]2[CH:35]=[C:34]([O:36][CH3:37])[C:33]([O:38][CH3:39])=[C:32]([O:40][CH3:41])[CH:31]=2)[C:14]([NH:16][CH2:17][C:18]2[CH:28]=[CH:27][C:21]([C:22]([NH:2][OH:3])=[O:23])=[CH:20][CH:19]=2)=[O:15])=[CH:11][CH:12]=1

Participants

7

Reactant 4

HCID 962WaterHCID 14797Potassium Hydroxide2×HCID 443297Hydroxyamine hydrochlorideHCID 68490940Ethyl 4-((2-(4-fluorophenyl)-3-(3,4,5-trimethoxyphenyl)acrylamido)methyl)benzoate

Product 1

HCID 744389434-((2-(4-fluorophenyl)-3-(3,4,5-trimethoxyphenyl)acrylamido)methyl)-N-hydroxybenzamideYield 52.9%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

Hydroxylamine hydrochloride (1.25 g, 18 mmol) in methanol (3 mL) was mixed with KOH (1.0 g, 18 mmol) in methanol (6 mL) at 0° C. and the reaction mixture was sonicated for 5 minutes. A white precipitate was formed which was filtered. The filtrate was immediately added to the ethyl 4-((2-(4-fluorophenyl)-3-(3,4,5-trimethoxyphenyl)acrylamido)methyl)benzoate (0.4 g, 1 mmol) followed by the addition of KOH (0.084 g, 1.5 mmol) and the mixture was stirred at room temperature for 1 hour. Around 20 mL of water was added to the reaction mixture and it was neutralized to pH 7 by addition of dilute acetic acid. Upon standing, a colorless precipitate was formed, it was filtered, dried and triturated with dichloromethane/hexanes (1:1, 20 mL), to afford the required compound as a pure colorless solid (0.254 g, 38% yield). 1H NMR (DMSO-d6) δ (ppm): 3.49 (61-1, s, —OCH3), 3.60 (3H, s, —OCH3), 4.36 (2H, d, —CH2), 6.32 (2H, s, Ar—H), 7.29-7.39 (6H, d, Ar—H), 7.48 (1H, s, ═CH), 7.69 (2H, d, Ar—H), 7.96 (1H, t, —NH), 8.99 (1H, s, —OH), 11.16 (1H, s, —NH); MS m/z: 497.1 (M++1).

Workup

  1. customthe reaction mixture was sonicated for 5 minutes
  2. customA white precipitate was formed which
  3. filtrationwas filtered
  4. customa colorless precipitate was formed
  5. filtrationit was filtered
  6. customdried
  7. customtriturated with dichloromethane/hexanes (1:1, 20 mL)

Sources & evidence

ORD record
ord-d43b6ae2fddf4856a7ae920c06fc9d4d
Source dataset
uspto-grants-2013_07
Patent number
US08476255B2

Reaction notes

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