Hydrochloric Acid → HCID 59199437, compound

HRID 2089552Notes

Reaction equation

HRID 2089552 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4](O)[C:5]([CH3:16])([CH3:15])[CH:6]2[O:11][C:12](=[O:14])[CH3:13].[NH:18]1[CH:22]=[C:21]([C:23]([O:25][CH3:26])=[O:24])[N:20]=[CH:19]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>[CH3:26][O:25][C:23]([C:21]1[N:20]([CH:4]2[C:3]3[C:7](=[CH:8][CH:9]=[CH:10][C:2]=3[Cl:1])[CH:6]([O:11][C:12](=[O:14])[CH3:13])[C:5]2([CH3:16])[CH3:15])[CH:19]=[N:18][CH:22]=1)=[O:24]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 97268Di-tert-butyl azodicarboxylateHCID 59199372HCID 59199372, compoundHCID 178418785HCID 178418785, compound

Product 1

HCID 59199437HCID 59199437, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of acetic acid 4-chloro-3-hydroxy-2,2-dimethyl-indan-1-yl ester (1.55 g, 6.1 mmol) in THF (30 mL) is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 1.53 g, 12.2 mmol), and triphenylphosphine (3.2 g, 12.2 mmol). The reaction is cooled to 0° C. and di-t-butyl azodicarboxylate (2.81 g, 12.2 mmol) is added. The reaction is placed at room temperature and permitted to stir for ca. 12 hours and then is heated to 40° C. for 1.5 hours. The reaction mixture is cooled to 0° C., quenched with 4 N HCl in dioxane (20 mL, 80 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 combined organic layers are dried with Na2SO4, filtered, and concentrated. The resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:3) to furnish 3-(3-acetoxy-7-chloro-2,2-dimethyl-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 332.04 (M+H)+.

Workup

  1. customis placed at room temperature
  2. temperatureis heated to 40° C. for 1.5 hours
  3. temperatureThe reaction mixture is cooled to 0° C.
  4. stirringstirred for 30 minutes
  5. concentrationThe reaction is concentrated
  6. additiondiluted with ethyl acetate
  7. extractionThe organic layer is extracted three times with 1 N aqueous HCl
  8. extractionextracted three times with ethyl acetate
  9. dry with materialThe combined organic layers are dried with Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting residue is purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0:1 to 1:3)

Sources & evidence

ORD record
ord-7fc4fbb775ee46c2b1bc106188dd80b9
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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