1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[3-cyclopropyl-2-(4-methoxy-phenyl)-3H-imidazol-4-yl]-2-methyl-acrylic acid ethyl ester

HRID 732100Notes

Reaction equation

HRID 732100 reaction equation
[CH:1]1([N:4]2[C:8]([CH:9]=O)=[CH:7][N:6]=[C:5]2[C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)[CH2:3][CH2:2]1.C([C:21](CC)(CC)[CH:22](P(O)(O)=O)[C:23]([O-:25])=[O:24])C.[CH2:34]1CCN2C(=NCCC2)C[CH2:35]1>C(#N)C.O>[CH2:34]([O:25][C:23](=[O:24])[C:22]([CH3:21])=[CH:9][C:8]1[N:4]([CH:1]2[CH2:3][CH2:2]2)[C:5]([C:11]2[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=2)=[N:6][CH:7]=1)[CH3:35]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 578380093-cyclopropyl-2-(4-methoxy-phenyl)-3H-imidazole-4-carbaldehydeHCID 92003523Triethyl-2-phosphonopropionate

Product 1

HCID 670709683-[3-cyclopropyl-2-(4-methoxy-phenyl)-3H-imidazol-4-yl]-2-methyl-acrylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
78 °C

Procedure

3-cyclopropyl-2-(4-methoxy-phenyl)-3H-imidazole-4-carbaldehyde (475 mg, 1.96 mmol), triethyl-2-phosphonopropionate (0.63 ml, 2.94 mmol) and DBU (0.44 ml, 2.94 mmol) were dissolved in acetonitrile (5 ml). After stirring at 78° C. o.n. the reaction mixture was cooled to r.t., diluted with water (50 ml) and extracted with DCM. The combined organic phase was dried (Na2SO4), filtered and concentrated, to yield 3-[3-cyclopropyl-2-(4-methoxy-phenyl)-3H-imidazol-4-yl]-2-methyl-acrylic acid ethyl ester, which was dissolved in ethanol and hydrogenated at atmospheric pressure over 10% Pd/C (0.5 g) for 24 h. The reaction mixture was filtered through a celite pad and concentrated. After purification on silica gel (EA/DCM=1/1) the isolated product was dissolved in Et2O (10 ml) and treated with HCl (1N in Et2O, 4 ml). The resulting mixture was concentrated and the isolated residue was triturated with Et2O to isolate the title compound solid (466 mg). 1H-NMR: 7.90 (d, 2H), 7.10 (m, 3H), 4.16 (m, 2H), 3.90 (s, 3H), 3.47 (m, 1H), 3.24 (m, 1H), 2.85 (m, 2H), 1.37 (d, 3H), 1.27 (m, 5H), 0.75 (m, 2H).

Workup

  1. temperaturethe reaction mixture was cooled to r.t.
  2. extractionextracted with DCM
  3. dry with materialThe combined organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-f29a44d505984f8f840b2f1a531434af
Source dataset
uspto-grants-2009_09
Patent number
US07585881B2

Reaction notes

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