Ammonia → (2E)-3-{4-[Cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenamide

HRID 229136Notes

Reaction equation

HRID 229136 reaction equation
[C:1]1(=[C:8]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=2)[C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17](O)=[O:18])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C(Cl)(=O)C(Cl)=O.ClCCl.[NH3:36]>C1(C)C=CC=CC=1.CN(C=O)C>[C:1]1(=[C:8]([C:20]2[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=2)[C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17]([NH2:36])=[O:18])=[CH:11][CH:10]=2)[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 222AmmoniaHCID 6344Dichloromethane3×HCID 65578Oxalyl chloride2×HCID 11314050(2E)-3-{4-[cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoic acid

Product 1

HCID 11314024(2E)-3-{4-[Cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalyst2×HCID 1140TolueneSolvent

Procedure

To a stirred suspension of (2E)-3-{4-[cycloheptylidene(4-hydroxyphenyl)methyl]phenyl}-2-propenoic acid (11) (0.23 g, 0.66 mmol) in toluene (6 mL) was slowly added oxalyl chloride (0.12 mL, 0.175 g, 1.38 mmol, 2.1 eq) followed by DMF (2-3 drops) at room temperature under a nitrogen atmosphere. The reaction mixture was stirred for 0.25 h. Dichloromethane (6 mL) was added to the reaction mixture (to aid the dissolution of solids) and the reaction mixture was stirred at room temperature for 2 h. Oxalyl chloride (0.12 mL, 0.175 g, 1.38 mmol, 2.1 eq) and DMF (2 drops) were added to the reaction mixture and stirring was continued for 3 h. The reaction mixture was concentrated in vacuo. Toluene was added to the crude acid chloride and the solvent was removed in vacuo. To the crude acid chloride were added ammonia (0.5 M in 1,4-dioxane) (6 mL, 3 mmol, 4.5 eq) followed by CH2Cl2 (5 mL). The reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere. The reaction mixture was transferred to a separatory funnel with the aid of CH2Cl2 and the solution was washed with water. The layers were separated and the organic phase was dried over MgSO4, filtered, and the filtrate was concentrated to give the crude amide as a gold-yellow oil. The crude product was purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 95:5) to give a solid which was dried at 70° C. under vacuum to give 0.058 g (25%) of compound 13 as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ 1.51 (m, 8H), 2.22 (m, 4H), 6.53 (d, J=15.9 Hz, 1H), 6.66 (d, J=8.5 Hz, 2H), 6.91 (d, J=8.3 Hz, 2H), 7.06 (br s, 1H), 7.12 (d, J=8.1 Hz, 2H), 7.35 (d, J=15.9 Hz, 1H), 7.45 (d, J=8.1 Hz, 2H), 7.50 (br s, 1H), 9.29 (s, 1H). HRMS (ESI) Calcd for C23H26NO2: 348.1964 (M+H)+. Found: 348.1951.

Workup

  1. dissolutionthe dissolution of solids) and the reaction mixture
  2. stirringwas stirred at room temperature for 2 h
  3. stirringstirring
  4. waitwas continued for 3 h
  5. concentrationThe reaction mixture was concentrated in vacuo
  6. additionToluene was added to the crude acid chloride
  7. customthe solvent was removed in vacuo
  8. stirringThe reaction mixture was stirred overnight at room temperature under a nitrogen atmosphere
  9. washthe solution was washed with water
  10. customThe layers were separated
  11. dry with materialthe organic phase was dried over MgSO4
  12. filtrationfiltered
  13. concentrationthe filtrate was concentrated

Sources & evidence

ORD record
ord-9ac0da3c0cac4829b022fa0a386138b5
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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