1,8-Diazabicyclo(5.4.0)undec-7-ene → ethyl 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)vinyl)-5-fluorobenzoate

HRID 83925Notes

Reaction equation

HRID 83925 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:11]2[N:15]([C:16]3[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=3)[C:14]([CH:23]=O)=[N:13][CH:12]=2)([CH3:10])[CH3:9])=[CH:4][C:3]=1[O:25][CH3:26].[Br-].[Cl:28][C:29]1[CH:54]=[C:53]([C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH:52]=[C:51]([F:60])[C:30]=1[CH2:31][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1CCN2C(=NCCC2)CC1>CC#N.O>[Cl:28][C:29]1[CH:54]=[C:53]([CH:52]=[C:51]([F:60])[C:30]=1[CH:31]=[CH:23][C:14]1[N:15]([C:16]2[CH:17]=[CH:18][C:19]([F:22])=[CH:20][CH:21]=2)[C:11]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([O:25][CH3:26])[CH:4]=2)([CH3:10])[CH3:9])=[CH:12][N:13]=1)[C:55]([O:57][CH2:58][CH3:59])=[O:56]

Participants

6

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 86662238(2-Chloro-4-(ethoxycarbonyl)-6-fluorobenzyl)triphenylphosphonium bromideHCID 86662240HCID 86662240, compound

Product 1

HCID 66740361ethyl 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)vinyl)-5-fluorobenzoateYield 51.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

To a mixture of 5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazole-2-carbaldehyde (304 mg, 0.815 mmol) and (2-chloro-4-(ethoxycarbonyl)-6-fluorobenzyl)triphenylphosphonium bromide (454 mg, 0.815 mmol) in MeCN (5 mL) was added dropwise DBU (136 mg, 0.896 mmol). After stirring at 50° C. overnight, the mixture was diluted with H2O and extracted with DCM. The combined extracts were dried (MgSO4), filtered, concentrated and purified by flash chromatography (20-90% EtOAc/hexanes) to yield ethyl 3-chloro-4-(2-(5-(2-(4-chloro-3-methoxyphenyl)propan-2-yl)-1-(4-fluorophenyl)-1H-imidazol-2-yl)vinyl)-5-fluorobenzoate (0.241 g, 51%) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 8.05-7.87 (m, 3H), 7.85-7.58 (m, 13H), 7.20 (tt, J=15.1, 7.1 Hz, 1H), 5.21 (d, J=15.0 Hz, 2H), 4.34 (dq, J=14.2, 7.1 Hz, 2H), 1.33 (dt, J=14.2, 7.1 Hz, 3H).

Workup

  1. extractionextracted with DCM
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash chromatography (20-90% EtOAc/hexanes)

Sources & evidence

ORD record
ord-11e1b3bdbec94b3da31d788a695a5083
Source dataset
uspto-grants-2014_09
Patent number
US08846739B2

Reaction notes

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