Hydrochloric Acid → HCID 59199345, compound

HRID 2089546Notes

Reaction equation

HRID 2089546 reaction equation
C([SiH2][O:6][C:7](C)(C)[C:8]1[N:12]([CH:13]2[C:21]3[C:16](=[CH:17][C:18]([Cl:22])=[CH:19][CH:20]=3)[CH:15]([OH:23])[C:14]2([CH3:25])[CH3:24])[CH:11]=[N:10][CH:9]=1)(C)(C)C.Cl>O1CCOCC1.C([O-])(O)=O.[Na+].[O-2].[Mn+4].[O-2]>[Cl:22][C:18]1[CH:17]=[C:16]2[C:21]([CH:13]([N:12]3[C:8]([CH2:7][OH:6])=[CH:9][N:10]=[CH:11]3)[C:14]([CH3:25])([CH3:24])[C:15]2=[O:23])=[CH:20][CH:19]=1

Participants

6

Reactant 2

HCID 313Hydrochloric AcidHCID 131730559HCID 131730559, compound

Product 1

HCID 59199345HCID 59199345, compound

Reagents, catalysts & solvents 3

HCID 178418406HCID 178418406, compoundCatalystHCID 312751,4-DioxaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 3-[5-(tert-butyl-dimethyl-silanyloxymethyl)-imidazol-1-yl]-6-chloro-2,2-dimethyl-indan-1-ol (400 mg, 0.98 mmol) in 1,4-dioxane (15 mL) is added manganese(IV) oxide (2.0 g, 20 mmol). The resulting heterogeneous solution is heated at 80° C. for 60 minutes, cooled to room temperature, filtered and concentrated. The resulting residue is then dissolved in methanol, cooled to 0° C. and treated with 4 N hydrochloric acid in 1,4-dioxane (1 mL, 4.0 mmol). The reaction is placed at room temperature and permitted to stir for 3 hours, at which time the reaction is cooled to 0° C. and diluted with saturated aqueous NaHCO3. The reaction mixture is then concentrated in vacuo to ca. one fourth of the original volume and diluted with ethyl acetate. The layers are separated and the aqueous layer is extracted two times with ethyl acetate. The combined organic extracts are dried over Na2SO4, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (ethanol-ethyl acetate, 0:1 to 1:10) to furnish 6-chloro-3-(5-hydroxymethyl-imidazol-1-yl)-2,2-dimethyl-indan-1-one; HRMS: (ESI) m/z 291.0891 [(M+H)+: Calcd for C15H16N2O2Cl: 291.0900]; 1H NMR (400 MHz, CDCl3) δ ppm 0.87 (s, 3 H), 1.44 (s, 3 H), 1.89 (br. s., 1 H), 4.70-4.92 (m, 2 H), 5.75 (s, 1 H), 6.92 (s, 1 H), 7.07 (s, 1 H), 7.41 (d, J=8.1 Hz, 1 H), 7.69 (dd, J=8.3, 2.0 Hz, 1 H), 7.87 (d, J=2.0 Hz, 1 H).

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered
  3. concentrationconcentrated
  4. dissolutionThe resulting residue is then dissolved in methanol
  5. temperaturecooled to 0° C.
  6. customis placed at room temperature
  7. temperatureis cooled to 0° C.
  8. concentrationThe reaction mixture is then concentrated in vacuo to ca. one fourth of the original volume
  9. additiondiluted with ethyl acetate
  10. customThe layers are separated
  11. extractionthe aqueous layer is extracted two times with ethyl acetate
  12. dry with materialThe combined organic extracts are dried over Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe resulting residue is purified by silica gel flash chromatography (ethanol-ethyl acetate, 0:1 to 1:10)

Sources & evidence

ORD record
ord-8701cd5d94954146a8cc0b8444e010f4
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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