Imidazole → HCID 59199365, compound

HRID 2089531Notes

Reaction equation

HRID 2089531 reaction equation
[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4](O)[CH2:3]1.[NH:13]1[CH:17]=[CH:16][N:15]=[CH:14]1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.CN(C)C(N=NC(N(C)C)=O)=O>C1(C)C=CC=CC=1.CCCCCCC>[CH3:1][C:2]1([CH3:12])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]([N:13]2[CH:17]=[CH:16][N:15]=[CH:14]2)[CH2:3]1

Participants

7

Reactant 4

HCID 795ImidazoleHCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 380203,3-Dimethyl-1-indanolHCID 83681Tris(1,1-dimethylethyl)phosphine

Product 1

HCID 59199365HCID 59199365, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8900HeptaneSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3,3-dimethyl-indan-1-ol (CAS#38393-92-9, 1.62 g, 1.0 mmol)] in toluene (30 mL) is added imidazole (1.36 g, 20.0 mmol) followed by tri-t-butylphosphine (2.5 mL, 10.1 mmol). The reaction is put at 0° C. and N,N,N′,N′-tetramethylazodicarboxamide (1.72 g, 10 mol) is then added. The reaction is permitted to stir for 10 minutes at 0° C. and then is heated at 60° C. over night. The next morning the reaction is diluted with heptane (30 mL) and filtered. The filtrate is extracted twice with 1 N aqueous HCl. The aqueous extracts are combined, washed with ethyl acetate and then basified (pH>10) by the careful addition of 5 N aqueous NaOH. The aqueous solution is then extracted three times with dichloromethane. The combined organic extracts are dried with Na2SO4. filtered and concentrated. The resulting residue is purified by semi-preparative reverse phase HPLC (15 to 85% acetonitrile/water w/0.1% NH4OH) to afford 1-(3,3-dimethyl-indan-1-yl)-1H-imidazole; HRMS: (ESI) m/z 213.1397 [(M+H)+; calcd for C14H17N2: 213.1392]; 1H NMR (400 MHz, CDCl3) δ ppm 1.28 (s, 3 H), 1.42 (s, 3 H), 2.11 (dd, J=12.9, 8.3 Hz, 1 H), 2.57 (dd, J=12.9, 7.6 Hz, 1 H), 5.72 (t, J=8.1 Hz, 1 H), 6.86 (s, 1 H), 7.01 (d, J=8.3 Hz, 1 H), 7.09 (s, 1 H), 7.19-7.29 (m, 2 H), 7.35 (t, J=7.5 Hz, 1 H), 7.62 (s, 1 H). 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-(3,3-dimethyl-indan-1-yl)-1H-imidazole.

Workup

  1. customis put at 0° C.
  2. temperatureis heated at 60° C. over night
  3. filtrationfiltered
  4. extractionThe filtrate is extracted twice with 1 N aqueous HCl
  5. washwashed with ethyl acetate
  6. additionby the careful addition of 5 N aqueous NaOH
  7. extractionThe aqueous solution is then extracted three times with dichloromethane
  8. dry with materialThe combined organic extracts are dried with Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue is purified by semi-preparative reverse phase HPLC (15 to 85% acetonitrile/water w/0.1% NH4OH)

Sources & evidence

ORD record
ord-8f3768ecbfe94f0aaea60bc860959e24
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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