Methanesulfonyl chloride → HCID 59199374, compound

HRID 2089544Notes

Reaction equation

HRID 2089544 reaction equation
[CH3:1][C:2]1([CH3:20])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1[N:11]1[C:15]([C:16](O)([CH3:18])[CH3:17])=[CH:14][N:13]=[CH:12]1.CS(Cl)(=O)=O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1.C(OCC)(=O)C.C([O-])(O)=O.[Na+].[Pd]>[CH3:1][C:2]1([CH3:20])[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]1[N:11]1[C:15]([CH:16]([CH3:17])[CH3:18])=[CH:14][N:13]=[CH:12]1

Participants

8

Reactant 2

HCID 31297Methanesulfonyl chlorideHCID 59199382HCID 59199382, compound

Product 1

HCID 59199374HCID 59199374, compound

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalystHCID 23938PalladiumCatalystHCID 1049PyridineSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 2-[3-(2,2-dimethyl-indan-1-yl)-3H-imidazol-4-yl]-propan-2-ol, which can be prepared as described in Example 22, (180 mg, 0.665 mmol) in pyridine (3 mL) is added 4-dimethylaminopyridine (50 mg, 0.4 mmol) and methanesulfonyl chloride (0.52 mL, 0.665 mmol). The reaction is permitted to stir for 90 minutes, at which time it is diluted with ethyl acetate and saturated aqueous NaHCO3. The layers are separated and the organic layer is dried with Na2SO4, filtered, and concentrated. The resulting residue is dissolved in ethanol (3 mL) and charged with 5% palladium on carbon (283 mg, 0.135 mmol). The reaction is placed under a hydrogen atmosphere (balloon pressure) for 1.5 hours, at which time it is filtered and the eluent concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:9) to provide 1-(2,2-dimethyl-indan-1-yl)-5-isopropyl-1H-imidazole. HRMS: (ESI) m/z 255.1870 [(M+H)+: Calcd for C17H23N2: 255.1861]; 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-isopropyl-1H-imidazole; 1H NMR (400 MHz, CD3OD) δ ppm 0.84 (s, 3 H), 1.33 (s, 3 H), 1.42 (d, J=6.6 Hz, 3 H), 1.49 (d, J=6.8 Hz, 3 H), 2.84-3.18 (m, 2 H), 3.23-3.32 (m, 1 H), 5.58 (s, 1 H), 7.24-7.48 (m, 4 H), 7.51 (s, 1 H), 8.19 (d, J=1.3 Hz, 1 H).

Workup

  1. customThe layers are separated
  2. dry with materialthe organic layer is dried with Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe resulting residue is dissolved in ethanol (3 mL)
  6. customfor 1.5 hours
  7. filtrationat which time it is filtered
  8. concentrationthe eluent concentrated
  9. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:9)

Sources & evidence

ORD record
ord-83cc42af284f487499efae77b32dc346
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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