Diisopropyl diazene-1,2-dicarboxylate → HCID 59199341, compound

HRID 2089467Notes

Reaction equation

HRID 2089467 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH:7](O)[CH2:6][CH2:5]2.[NH:12]1[CH:16]=[C:15]([C:17]([O:19][CH3:20])=[O:18])[N:14]=[CH:13]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1.C(OCC)(=O)C>[CH3:20][O:19][C:17]([C:15]1[N:14]([CH:7]2[C:8]3[C:4](=[CH:3][C:2]([F:1])=[CH:10][CH:9]=3)[CH2:5][CH2:6]2)[CH:13]=[N:12][CH:16]=1)=[O:18]

Participants

6

Reactant 3

HCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 230828905-Fluoro-2,3-dihydro-1H-inden-1-olHCID 178418785HCID 178418785, compound

Product 1

HCID 59199341HCID 59199341, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 5-fluoro-indan-1-ol (0.293 g, 1.925 mmol) and methyl 4-imidazolecarboxylate (CAS#17325-26-7, 0.163 g, 1.290 mmol) in THF (10 mL) at 0° C. is added pMe2NPhP(Ph)2 (0.619 g, 1.925 mmol) and diisopropyl azodicarboxylate (94%, 0.414 g, 1.925 mmol). After 1 hour the mixture is warmed to room temperature and after 18 hours it is diluted with ethyl acetate and extracted with 1M aqueous HCl. The extracts are cooled to 0° C., and the pH is adjusted to ca. 9 with ice-cold 4M aqueous NaOH. The basic aqueous phase is extracted three times with dichloromethane, and the combined organic phases are dried over magnesium sulfate, filtered through a cotton plug, and concentrated. The resulting residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 1:0 to 99:1 to 49:1) to afford 3-(5-fluoro-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 261.0 (M+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 3-(5-fluoro-indan-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; 1H NMR (400 MHz, CDCl3) δ ppm 2.06-2.20 (m, 1 H), 2.71-2.85 (m, 1 H), 2.87-3.00 (m, 1 H), 3.00-3.14 (m, 1 H), 3.87 (s, 3 H), 6.47 (dd, J=7.7, 4.7 Hz, 1 H), 6.88-6.97 (m, 1 H), 7.01 (dd, J=8.6, 2.3 Hz, 1 H), 7.16 (dd, J=8.6, 5.1 Hz, 1 H), 7.19 (s, 1 H), 7.77 (s, 1 H).

Workup

  1. extractionextracted with 1M aqueous HCl
  2. temperatureThe extracts are cooled to 0° C.
  3. extractionThe basic aqueous phase is extracted three times with dichloromethane
  4. dry with materialthe combined organic phases are dried over magnesium sulfate
  5. filtrationfiltered through a cotton plug
  6. concentrationconcentrated
  7. customThe resulting residue is purified by silica gel flash chromatography (elution with dichloromethane-methanol, 1:0 to 99:1 to 49:1)

Sources & evidence

ORD record
ord-f5d9827c4ad34a7aa0f5c99de0a764e7
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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