Ammonia → (2E)-3-{4-[(4-Hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenamide

HRID 229140Notes

Reaction equation

HRID 229140 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:20]2[CH2:25][C:24]([CH3:27])([CH3:26])[CH2:23][C:22]([CH3:29])([CH3:28])[CH2:21]2)[C:9]2[CH:14]=[CH:13][C:12](/[CH:15]=[CH:16]/[C:17](O)=[O:18])=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[NH3:36]>C(Cl)Cl.CN(C=O)C>[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[C:20]2[CH2:25][C:24]([CH3:27])([CH3:26])[CH2:23][C:22]([CH3:29])([CH3:28])[CH2:21]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)=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 222AmmoniaHCID 65578Oxalyl chlorideHCID 11303858(2E)-3-{4-[(4-Hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenoic acid

Product 1

HCID 11463422(2E)-3-{4-[(4-Hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenamideYield 15%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideCatalystHCID 6344DichloromethaneSolvent

Procedure

To a stirred suspension of (2E)-3-{4-[(4-hydroxyphenyl)(3,3,5,5-tetramethylcyclohexylidene)methyl]phenyl}-2-propenoic acid (16) (0.18 g, 0.46 mmol) in CH2Cl2 (6 mL) at room temperature was added oxalyl chloride (0.15 mL, 0.218 g, 1.72 mmol, 3.7 eq) followed by several drops of DMF (Note: vigorous bubbling occurred upon addition of DMF). The reaction mixture was stirred under a nitrogen atmosphere for 1 h and concentrated in vacuo. Toluene was added to the crude acid chloride and the solvent was removed in vacuo. To the crude acid chloride was added ammonia (0.5 M in 1,4-dioxane) (6 mL) and the turbid reaction mixture stirred at room temperature under a nitrogen atmosphere for 3 h. Ammonia (0.5 M in 1,4-dioxane) (2 mL) was added to the reaction mixture and stirring was continued overnight at room temperature under a nitrogen atmosphere. The reaction mixture was concentrated in vacuo. Ammonia (0.5 M in 1,4-dioxane) (8 mL) and CH2Cl2 (8 mL) were added to the residue. The flask was equipped with a rubber septum and the reaction mixture was stirred at room temperature for 2 d. The reaction mixture was transferred to a separatory funnel and partitioned between CH2Cl2 and H2O. The layers were separated and the aqueous phase was extracted with CH2Cl2. The organic extracts were combined, washed with brine, dried (MgSO4) filtered, and the filtrate was concentrated to give the crude product as an amorphous solid. The crude product was purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 19:1) as eluant to provide the product which was dried to give 0.026 g (15%) of compound 17 as a pale yellow solid. 1H NMR (400 MHz, DMSO-d6): δ 0.87 (s, 6H), 0.88 (s, 6H), 1.25 (s, 2H), 1.89 (s, 2H), 1.92 (s, 2H), 6.53 (d, J=15.8 Hz, 1H), 6.66 (d, J=8.5 Hz, 2H), 6.93 (d, J=8.5 Hz, 2H), 7.06 (br s, 1), 7.14 (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), 9.30 (s, 1). HRMS (ESI) Calcd for C26H32 NO2: 390.2433 (M+H)+. Found: 390.2427.

Workup

  1. concentrationconcentrated in vacuo
  2. additionToluene was added to the crude acid chloride
  3. customthe solvent was removed in vacuo
  4. additionTo the crude acid chloride was added ammonia (0.5 M in 1,4-dioxane) (6 mL)
  5. customthe turbid reaction mixture
  6. stirringstirred at room temperature under a nitrogen atmosphere for 3 h
  7. stirringstirring
  8. waitwas continued overnight at room temperature under a nitrogen atmosphere
  9. concentrationThe reaction mixture was concentrated in vacuo
  10. additionAmmonia (0.5 M in 1,4-dioxane) (8 mL) and CH2Cl2 (8 mL) were added to the residue
  11. customThe flask was equipped with a rubber septum
  12. stirringthe reaction mixture was stirred at room temperature for 2 d
  13. customThe reaction mixture was transferred to a separatory funnel
  14. custompartitioned between CH2Cl2 and H2O
  15. customThe layers were separated
  16. extractionthe aqueous phase was extracted with CH2Cl2
  17. washwashed with brine
  18. dry with materialdried (MgSO4)
  19. filtrationfiltered
  20. concentrationthe filtrate was concentrated
  21. customto give the crude product as an amorphous solid
  22. customThe crude product was purified by flash chromatography on silica gel with CH2Cl2:MeOH (100:0 to 19:1) as eluant
  23. customto provide the product which
  24. customwas dried

Sources & evidence

ORD record
ord-f53c8d858a8c4e4b986c64b7cd501813
Source dataset
uspto-grants-2009_07
Patent number
US07560589B2

Reaction notes

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