1,2,3,4-Tetrahydro-1-naphthalenol → 3-(1,2,3,4-Tetrahydronaphthalen-1-YL)-3H-imidazole-4-carboxylic acid methyl ester

HRID 2089465Notes

Reaction equation

HRID 2089465 reaction equation
[CH:1]1(O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH2:4][CH2:3][CH2:2]1.[NH:12]1[CH:16]=[C:15]([C:17]([O:19][CH3:20])=[O:18])[N:14]=[CH:13]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=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:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH2:4][CH2:3][CH2:2]2)[CH:13]=[N:12][CH:16]=1)=[O:18]

Participants

7

Reactant 4

HCID 107231,2,3,4-Tetrahydro-1-naphthalenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 178418785HCID 178418785, compound

Product 1

HCID 144976243-(1,2,3,4-Tetrahydronaphthalen-1-YL)-3H-imidazole-4-carboxylic acid methyl ester

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,2,3,4-tetrahydro-1-naphthol (CAS#529-33-9, 1.00 g, 6.74 mmol), which can be prepared as described in Ollivier, R.; et al. Journal of Medicinal Chemistry, 1997, 40, 952-960, in THF (60 mL), at 0° C. is added methyl 4-imidazolecarboxylate (CAS#17325-26-7, 0.85 g, 6.74 mmol) and triphenylphosphine, followed by diisopropyl azodicarboxylate (1.36 g, 6.74 mmol). The cooling bath is then removed. After 16 hours, the solvent is evaporated in vacuo and the residue is purified by silica gel flash chromatography (elution with ethyl acetate) to give a partially purified product, which is dissolved in ethyl acetate and extracted with 1M aqueous HCl. The aqueous layer is basified to a pH of ca. 9 with 2M aqueous NaOH, and then extracted three times with dichloromethane. The organic layers are combined, dried with MgSO4, filtered, and concentrated to furnish 3-(1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; MS: (ESI) m/z 257.2 (M+H)+. The HNO3 salt of the title compound is prepared by dissolving the free base in methanol, followed by treatment with an excess of a 1:1 solution of HNO3—H2O. Concentration and trituration with diethyl ether and methanol, provides the nitric acid salt of 3-(1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid methyl ester; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.66-1.87 (m, 2 H), 2.11-2.33 (m, 2 H), 2.81 (dt, J=17.2, 6.5 Hz, 1 H), 2.93 (dt, J=17.2, 6.0 Hz, 1 H), 3.87 (s, 3 H), 6.33 (t, J=5.9 Hz, 1 H), 6.99 (d, J=7.6 Hz, 1 H), 7.10-7.21 (m, 1 H), 7.21-7.35 (m, 2 H), 8.34 (s, 1 H), 8.58 (s, 1 H).

Workup

  1. customThe cooling bath is then removed
  2. customthe solvent is evaporated in vacuo
  3. customthe residue is purified by silica gel flash chromatography (elution with ethyl acetate)
  4. customto give a partially purified product, which
  5. extractionextracted with 1M aqueous HCl
  6. extractionextracted three times with dichloromethane
  7. dry with materialdried with MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-c410ecbcd73847fb93d1a7b145f4ba3e
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

Loading…