Toluene → 1-(2,2-dimethyl-indan-1-yl)-5-trifluoromethyl-1H-imidazole

HRID 2089520Notes

Reaction equation

HRID 2089520 reaction equation
[CH3:1][C:2]1([CH3:12])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1O.[F:13][C:14]([F:21])([F:20])[C:15]1[NH:19][CH:18]=[N:17][CH:16]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC)=O)=NC(OC)=O.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>C1COCC1.C(OCC)C.O>[CH3:1][C:2]1([CH3:12])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1[N:19]1[C:15]([C:14]([F:21])([F:20])[F:13])=[CH:16][N:17]=[CH:18]1

Participants

10

Reactant 6

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 351621Azodicarboxylic acid dimethyl esterHCID 5858914(5)-(Trifluoromethyl)imidazoleHCID 109427712,3-Dihydro-2,2-dimethyl-1H-inden-1-ol

Product 1

HCID 591993601-(2,2-dimethyl-indan-1-yl)-5-trifluoromethyl-1H-imidazole

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2,2-dimethyl-indan-1-ol, prepared as described in Example 10, (400 mg, 2.47 mmol) in THF (30 mL) at 0° C. is added 5-trifluoromethyl-1H-imidazole (510 mg, 3.75 mmol), triphenylphosphine (982 mg, 3.75 mmol) and a 40 wt % solution of dimethyl azodicarboxylate in toluene (1.4 mL, 3.75 mmol). The reaction is then placed at room temperature and permitted to stir for 1 hour, at which time it is diluted with diethyl ether and water, and is then charged with Na2CO3 (1.9 g, 17.9 mmol). The reaction is permitted to stir for 10 minutes and the layers are separated. The organic layer is washed with brine and the aqueous layers are combined and back-extracted with diethyl ether. The organic layers are combined, dried with MgSO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes, 15:85 to 1:1) to afford 1-(2,2-dimethyl-indan-1-yl)-5-trifluoromethyl-1H-imidazole; HRMS: (ESI) m/z 281.1266 [(M+H)+; calcd for C15H15F3N3: 281.1276]. The HCl salt of the title compound can be prepared by dissolution in diethyl ether, followed by treatment with an excess of 1N HCl in diethyl ether. The resulting heterogeneous solution is concentrated to furnish the HCl salt of 1-(2,2-dimethyl-indan-1-yl)-5-trifluoromethyl-1H-imidazole; 1H NMR (400 MHz, CD3OD) δ ppm 0.91 (s, 3 H), 1.29 (s, 3 H), 2.83-3.24 (m, 2 H), 5.46 (s, 1 H), 7.25-7.50 (m, 4 H), 8.12 (s, 1 H), 8.18 (s, 1 H).

Workup

  1. customis then placed at room temperature
  2. stirringto stir for 10 minutes
  3. customthe layers are separated
  4. washThe organic layer is washed with brine
  5. extractionback-extracted with diethyl ether
  6. dry with materialdried with MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-hexanes, 15:85 to 1:1)

Sources & evidence

ORD record
ord-93bd008a4233480bbeb46aba5584d7a1
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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