Sodium Bicarbonate → tert-butyl 2-(1-(4-bromophenyl)-2-(2-(2-chlorophenyl)propan-2-yl)-1H-imidazol-4-yl)pyrrolidine-1-carboxylate

HRID 1673025Notes

Reaction equation

HRID 1673025 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[NH:20])[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])([CH3:12])[CH3:11])=[CH:4][CH:3]=1.I[CH2:22][C:23]([CH:25]1[CH2:29][CH2:28][CH2:27][N:26]1[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=O.C([O-])(O)=O.[Na+]>O1CCOCC1>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH:22]=[C:23]([CH:25]3[CH2:29][CH2:28][CH2:27][N:26]3[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[N:20]=[C:9]2[C:10]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[Cl:19])([CH3:12])[CH3:11])=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 57458742HCID 57458742, compoundHCID 178449869HCID 178449869, compound

Product 1

HCID 67339382tert-butyl 2-(1-(4-bromophenyl)-2-(2-(2-chlorophenyl)propan-2-yl)-1H-imidazol-4-yl)pyrrolidine-1-carboxylateYield 5.5%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of N-(4-bromophenyl)-2-(2-chlorophenyl)-2-methylpropanimidamide (3.51 g, 10 mmol) in 60 mL dioxane was added tert-butyl 2-(2-iodoacetyl)pyrrolidine-1-carboxylate (3.38 g, 10 mmol) and NaHCO3 (2.5 g, 30 mmol). The mixture was heated to reflux with stirring for 2 days. The reaction was monitored by LC/MS. The reaction mixture was cooled and filtered over celite. The crude mixture was initially purified by silica gel column chromatography. The fraction containing the desired product was further purified by prep HPLC, affording 300 mg (5.5%) of tert-butyl 2-(1-(4-bromophenyl)-2-(2-(2-chlorophenyl)propan-2-yl)-1H-imidazol-4-yl)pyrrolidine-1-carboxylate. 1H NMR (CD3OD): δ 1.4 (m, 10H), 1.6 (m, 3H,), 1.8 (m, 1H), 1.9-2.3 (m, 5H), 3.4 (m, 1H), 3.6 (m, 1H) 4.6 (m, 1H), 6.9 (m, 3H), 7.05 (m, 1H), 7.2 (m, 2H), 7.25 (m, 1H), 7.50 (m, 2H); LC/MS M+H 544 (observed).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. temperatureThe reaction mixture was cooled
  4. filtrationfiltered over celite
  5. customThe crude mixture was initially purified by silica gel column chromatography
  6. additionThe fraction containing the desired product
  7. customwas further purified by prep HPLC

Sources & evidence

ORD record
ord-110048fcb3f9474ca3963844fa53457b
Source dataset
uspto-grants-2011_08
Patent number
US07998995B2

Reaction notes

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