Pyridine → propan-2-yl 3-[(4E)-7-methoxy-4-methoxyimino-2,2-dimethyl-1,3-dihydronaphthalen-1-yl]imidazole-4-carboxylate

HRID 2089528Notes

Reaction equation

HRID 2089528 reaction equation
[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=3)[C:15](=O)[CH2:14][C:13]2([CH3:26])[CH3:25])[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:3])[CH3:2].Cl.[CH3:28][O:29][NH2:30].N1C=CC=CC=1>C(O)(C)C.C(OCC)(=O)C>[CH:1]([O:4][C:5]([C:7]1[N:8]([CH:12]2[C:21]3[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH3:23])[CH:20]=3)/[C:15](=[N:30]/[O:29][CH3:28])/[CH2:14][C:13]2([CH3:25])[CH3:26])[CH:9]=[N:10][CH:11]=1)=[O:6])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 1049PyridineHCID 521874O-Methylhydroxylamine hydrochlorideHCID 591993943-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester

Product 1

HCID 59199326propan-2-yl 3-[(4E)-7-methoxy-4-methoxyimino-2,2-dimethyl-1,3-dihydronaphthalen-1-yl]imidazole-4-carboxylate

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 3-(7-methoxy-2,2-dimethyl-4-oxo-1,2,3,4-tetrahydro-naphthalen-1-yl)-3H-imidazole-4-carboxylic acid isopropyl ester, which can be prepared as described in Example 14, (0.053 g, 0.147 mmol) and methoxyamine hydrochloride (0.038 g, 0.442 mmol) in isopropanol (1 mL) is added pyridine (0.118 g, 1.472 mmol). The mixture is heated to 50° C. and after 2 hours, is diluted with ethyl acetate, and washed twice with 1M aqueous sodium bisulfate, water, and brine. The organic phase is dried over MgSO4, filtered and concentrated. The resulting residue is purified by silica gel flash chromatography (elution with heptane-ethyl acetate, 4:1 to 7:3) to give 3-{7-methoxy-4-[(E)-methoxyimino]-2,2-dimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl}-3H-imidazole-4-carboxylic acid isopropyl ester; MS: (ESI) m/z 386.0 (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-{7-Methoxy-4-[(E)-methoxyimino]-2,2-dimethyl-1,2,3,4-tetrahydro-naphthalen-1-yl}-3H-imidazole-4-carboxylic acid isopropyl ester; 1H NMR (400 MHz, MeOD) δ ppm 0.96 (s, 3 H), 1.12 (s, 3 H), 1.47 (d, J=6.1 Hz, 3 H), 1.49 (d, J=6.3 Hz, 3 H), 2.43 (d, J=17.9 Hz, 1 H), 3.01 (d, J=17.9 Hz, 1 H), 3.82 (s, 3 H), 4.04 (s, 3 H), 5.40 (sept, J=6.3 Hz, 1 H), 6.65 (s, 1 H), 6.79 (d, J=2.5 Hz, 1 H), 7.09 (dd, J=9.1, 2.5 Hz, 1 H), 8.16 (d, J=9.1 Hz, 1 H), 8.30 (s, 1 H), 8.53 (s, 1 H).

Workup

  1. washwashed twice with 1M aqueous sodium bisulfate, water, and brine
  2. dry with materialThe organic phase is dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe resulting residue is purified by silica gel flash chromatography (elution with heptane-ethyl acetate, 4:1 to 7:3)

Sources & evidence

ORD record
ord-6eec109239144dedb8fbe82f0473e5a5
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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