Ethyl Acetate → N-Hydroxy-7-methoxy-[4-(N,N-dimethylamino)phenyl]-2,4-heptadienamide

HRID 1182450Notes

Reaction equation

HRID 1182450 reaction equation
CO[CH:3]([C:12]1[CH:17]=[CH:16][C:15]([N:18]([CH3:20])[CH3:19])=[CH:14][CH:13]=1)[CH2:4][CH:5]=[CH:6][CH:7]=[CH:8]C(O)=O.[C:21]([N:28]1C=CN=C1)(N1C=CN=C1)=[O:22].[Si](N[OH:41])(C(C)(C)C)(C)C.[C:42](OCC)(=[O:44])C>C1COCC1.O>[OH:41][NH:28][C:21](=[O:22])[C:3]([C:12]1[CH:13]=[CH:14][C:15]([N:18]([CH3:19])[CH3:20])=[CH:16][CH:17]=1)=[CH:4][CH:5]=[CH:6][CH2:7][CH2:8][O:44][CH3:42]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 17809443t-ButyldimethylsilylhydroxylamineHCID 724803387-Methoxy-7-[4-(N,N-dimethylamino)phenyl]-2,4-heptadienoic acid

Product 1

HCID 86632630N-Hydroxy-7-methoxy-[4-(N,N-dimethylamino)phenyl]-2,4-heptadienamideYield 38%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of carboxylic acid 16 (110 mg, 0.40 mmol) in anhydrous THF (5 mL) was added 1,1′-carbonyldiimidazole (77 mg, 0.439 mmol) at rt, and the mixture was stirred overnight. To this solution was added t-butyldimethylsilylhydroxylamine (200 mg, 1.36 mmol). The mixture was stirred at rt for 14 h and then at 45° C. for 3 h. The resulting yellow solution was diluted with water (5 mL), stirred for 20 minutes, and then extracted with ethyl acetate (3×15 mL), dried, and concentrated. Purification by flash silica gel chromatography (80% ethyl acetate in hexanes and then ethyl acetate only) afforded the title compound 17 (44 mg, 38% yield): 1H NMR (300 MHz, CDCl3) δ 7.18 (dd, J=15.0, 10.2 Hz, 1H), 7.13 (d, J=8.7 Hz, 1H), 6.71 (d, J=8.7 Hz, 2H), 5.96-6.17 (m, 2H), 5.66 (br d, J=15.0 Hz, 1H), 4.09 (dd, J=7.5, 5.7 Hz, 1H), 3.17(s, 3H ), 2.94 (s, 6H), 2.61 (m, 1H),2.43 (m, 1H); 13C NMR (75.4 MHz, CDCl3) δ 40.6, 41.5, 56.2, 82.9, 112.4, 117.4, 127.6, 128.7, 130.1, 139.9, 141.9, 150.3, 165.5.

Workup

  1. stirringThe mixture was stirred at rt for 14 h
  2. waitat 45° C. for 3 h
  3. stirringstirred for 20 minutes
  4. extractionextracted with ethyl acetate (3×15 mL)
  5. customdried
  6. concentrationconcentrated
  7. customPurification by flash silica gel chromatography (80% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-c4235e0980d54a7b9b7a8b99844e072f
Source dataset
uspto-grants-2007_10
Patent number
US07288567B2

Reaction notes

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