Hydrochloric Acid → HCID 67546723, compound

HRID 2089549Notes

Reaction equation

HRID 2089549 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:10]=1[C:9](=[O:11])[C:8]([CH3:13])([CH3:12])[CH:7]2O.[NH:15]1[CH:19]=[C:18]([C:20]([O:22][CH3:23])=[O:21])[N:17]=[CH:16]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.Cl.O1CCOCC1>C1COCC1>[CH3:23][O:22][C:20]([C:18]1[N:17]([CH:7]2[C:6]3[C:10](=[C:2]([Cl:1])[CH:3]=[CH:4][CH:5]=3)[C:9](=[O:11])[C:8]2([CH3:13])[CH3:12])[CH:16]=[N:15][CH:19]=1)=[O:21]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 97268Di-tert-butyl azodicarboxylateHCID 59199367HCID 59199367, compoundHCID 178418785HCID 178418785, compound

Product 1

HCID 67546723HCID 67546723, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 7-chloro-3-hydroxy-2,2-dimethyl-indan-1-one (1.10 g, 5.24 mmol) in THF (50 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 1.0 g, 7.85 mmol), followed by triphenylphosphine (2.1 g, 7.85 mmol). The reaction is cooled to 0° C. and di-t-butyl azodicarboxylate (1.8 g, 7.85 mmol) is added. The reaction is permitted to warm to room temperature and stirred for 2 hours. The reaction mixture is then cooled to 0° C., quenched with 4 N HCl in dioxane (5 mL, 20 mmol) and stirred for 30 minutes. The reaction is concentrated to near dryness and diluted with ethyl acetate. The organic layer is extracted three times with 1 N aqueous HCl. The aqueous extracts are combined, neutralized with Na2CO3, and extracted three times with ethyl acetate. The organic layers are combined, dried over Na2SO4, filtered concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:1) to furnish 3-(4-chloro-2,2-dimethyl-3-oxo-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 319.0 (M+H)+

Workup

  1. temperatureto warm to room temperature
  2. temperatureThe reaction mixture is then cooled to 0° C.
  3. stirringstirred for 30 minutes
  4. concentrationThe reaction is concentrated
  5. additiondiluted with ethyl acetate
  6. extractionThe organic layer is extracted three times with 1 N aqueous HCl
  7. extractionextracted three times with ethyl acetate
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-heptane, 0:1 to 1:1)

Sources & evidence

ORD record
ord-693c31488b7c45b1b5147d6e73b826a2
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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