Potassium Hydroxide → N-cyclopropyl-2-(4-fluorophenyl)-3-(4-((E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)acrylamide

HRID 2098566Notes

Reaction equation

HRID 2098566 reaction equation
Cl.[NH2:2][OH:3].[OH-].[K+].[CH:6]1([NH:9][C:10](=[O:32])[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[CH:12][C:13]2[CH:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[C:21](OC)=[O:22])=[CH:15][CH:14]=2)[CH2:8][CH2:7]1>CO.C(Cl)Cl.O>[CH:6]1([NH:9][C:10](=[O:32])[C:11]([C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)=[CH:12][C:13]2[CH:18]=[CH:17][C:16](/[CH:19]=[CH:20]/[C:21]([NH:2][OH:3])=[O:22])=[CH:15][CH:14]=2)[CH2:8][CH2:7]1

Participants

7

Reactant 3

HCID 14797Potassium HydroxideHCID 443297Hydroxyamine hydrochlorideHCID 68766754methyl 3-(E)(4-(3-(cyclopropylamino)-2-(4-fluorophenyl)-3-oxoprop-1-en-1-yl)phenyl)acrylate

Product 1

HCID 86761863N-cyclopropyl-2-(4-fluorophenyl)-3-(4-((E)-3-(hydroxyamino)-3-oxoprop-1-en-1-yl)phenyl)acrylamideYield 28.1%

Reagents, catalysts & solvents 3

HCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

Hydroxylamine hydrochloride (0.86 g, 12.3 mmol) in methanol (3 mL) was mixed with KOH (0.69 g, 12.3 mmol) in methanol (3 mL) at 0° C., and sonicated for 2 minutes, the white precipitate formed was filtered. The filtrate was added to methyl 3-(E)(4-(3-(cyclopropylamino)-2-(4-fluorophenyl)-3-oxoprop-1-en-1-yl)phenyl)acrylate (0.25 g, 0.68 mmol) in DCM (1.5 mL) and the mixture was stirred at room temperature, for 30 minutes. The reaction mixture was diluted with water (200 mL) and extracted with ethyl acetate (2×150 mL). The ethyl acetate layer was dried over anhydrous Na2SO4 and concentrated to obtain a sticky compound, which was triturated with DCM (15 mL). The pale brown solid obtained was filtered and washed with DCM (3×5 mL) to afford the title compound (0.07 g, 28% yield). 1H NMR (DMSO-d6) δ (ppm): 0.49-0.53 (2H, dd, —CH2), 0.61-0.66 (2H, m, —CH2), 2.72-2.77 (1H, m, —CH), 6.38-6.42 (1H, d, ═CH), 7.00-7.02 (2H, d, Ar—H), 7.16-7.27 (5H, m, Ar—H and ═CH), 7.33-7.43 (3H, m, Ar—H and ═CH), 7.81-7.82 (1H, d, —NH), 9.04 (1H, s, —OH), 10.73 (1H, s, —NH). MS m/z: 367.1 (M++1).

Workup

  1. customsonicated for 2 minutes
  2. customthe white precipitate formed
  3. filtrationwas filtered
  4. extractionextracted with ethyl acetate (2×150 mL)
  5. dry with materialThe ethyl acetate layer was dried over anhydrous Na2SO4
  6. concentrationconcentrated
  7. customto obtain a sticky compound, which
  8. customwas triturated with DCM (15 mL)
  9. customThe pale brown solid obtained
  10. filtrationwas filtered
  11. washwashed with DCM (3×5 mL)

Sources & evidence

ORD record
ord-a897707854634858aed52edec8711fe6
Source dataset
uspto-grants-2013_05
Patent number
US08450525B2

Reaction notes

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