Hydrochloric Acid → HCID 178456400, compound

HRID 1004768Notes

Reaction equation

HRID 1004768 reaction equation
Cl.[C:2]([N:4]=[C:5]([NH:26][CH2:27][CH:28](OC)OC)[NH:6][CH2:7][CH:8]([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH:17]([F:19])[F:18])=[C:12]([O:20][CH:21]2[CH2:25][CH2:24][O:23][CH2:22]2)[CH:11]=1)[CH3:9])#[N:3].C1COCC1.[OH-].[Na+]>O1CCOCC1.O>[F:18][CH:17]([F:19])[O:16][C:13]1[CH:14]=[CH:15][C:10]([CH:8]([CH3:9])[CH2:7][N:6]2[CH:28]=[CH:27][NH:26][C:5]2=[N:4][C:2]#[N:3])=[CH:11][C:12]=1[O:20][CH:21]1[CH2:25][CH2:24][O:23][CH2:22]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 178495969HCID 178495969, compound

Product 1

HCID 178456400HCID 178456400, compoundYield 15.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Procedure

HCl 0.5 N (0.0162 mol) was added dropwise to a solution of intermediate 12 (0.0108 mol) in 1,4-dioxane (20 ml), stirred and cooled in an ice-bath. The reaction mixture was stirred for 2 days at RT. (As an alternative, 1,4-dioxane may be replaced by THF and the reaction mixture may be refluxed for 1 hour instead of stirring 2 days at RT). The reaction mixture was treated with water, alkalized with a dilute NaOH solution, then extracted with ethylacetate. The separated organic layer was dried, filtered, and the solvent was evaporated. The residue was purified by open column chromatography over silica gel (eluent: CH2C2 /2-propanone 96/4; CH2Cl2 /CH3OH 96/4) and twice by HPLC over silica gel (1. Eluent: CH2Cl2 /CH3OH 96/4 and 2. Eluent: CH2Cl2 /CH3OH 97/3). The pure fractions were collected and the solvent was evaporated, yielding 0.64 g (15%) of (±)-[1-[2-[4-(difluoromethoxy)-3-[(tetrahydro-3-furanyl)oxy]phenyl]-propyl]-1,3-dihydro-2H-imidazol-2-ylidene]cyanamide (compound 2; mp. 67.8° C.).

Workup

  1. temperaturecooled in an ice-bath
  2. stirringThe reaction mixture was stirred for 2 days at RT
  3. temperaturethe reaction mixture may be refluxed for 1 hour instead
  4. stirringof stirring 2 days at RT)
  5. extractionextracted with ethylacetate
  6. customThe separated organic layer was dried
  7. filtrationfiltered
  8. customthe solvent was evaporated
  9. customThe residue was purified by open column chromatography over silica gel (eluent: CH2C2 /2-propanone 96/4; CH2Cl2 /CH3OH 96/4) and twice by HPLC over silica gel (1. Eluent: CH2Cl2 /CH3OH 96/4 and 2. Eluent: CH2Cl2 /CH3OH 97/3)
  10. customThe pure fractions were collected
  11. customthe solvent was evaporated

Sources & evidence

ORD record
ord-a408319594d644c98ae5ca7947cd0b85
Source dataset
uspto-grants-2000_04
Patent number
US06051718

Reaction notes

Loading…