Hydrochloric Acid → HCID 74382623, compound

HRID 2089541Notes

Reaction equation

HRID 2089541 reaction equation
C([SiH2][O:6][C:7](C)(C)[C:8]1[N:12]([CH:13]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:15](=O)[C:14]2([CH3:24])[CH3:23])[CH:11]=[N:10][CH:9]=1)(C)(C)C.N1C=CC=CC=1.Cl.[CH2:34]([O:36][NH2:37])[CH3:35].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.C1COCC1>C(O)C.[NH4+].[Cl-].C(OCC)(=O)C>[CH2:34]([O:36][N:37]=[C:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:13]([N:12]2[C:8]([CH2:7][OH:6])=[CH:9][N:10]=[CH:11]2)[C:14]1([CH3:24])[CH3:23])[CH3:35]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 8028TetrahydrofuranHCID 69357Hydroxylamine, O-ethyl-HCID 2724141Tetrabutylammonium FluorideHCID 131730557HCID 131730557, compound

Product 1

HCID 74382623HCID 74382623, compound

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolvent

Procedure

To a solution of 3-[5-(tert-butyl-dimethyl-silanyloxymethyl)-imidazol-1-yl]-2,2-dimethyl-indan-1-one (1.07 g, 2.9 mmol), which can be prepared as described in Example 21, in ethanol (30 mL) is added pyridine (4.7 mL, 58 mmol) followed by the HCl salt of O-ethyl-hydroxylamine (850 mg, 8.7 mmol). The reaction is then heated at reflux for 1 hour, at which time it is cooled to room temperature and concentrated to near dryness. The resulting residue is diluted with ethyl acetate and washed with saturated aqueous NaHCO3. The organic layer is dried with Na2SO4, filtered, and concentrated. The resulting residue is taken directly to the next step, wherein it is dissolved in THF (30 mL) and then treated with a 1N solution of tetrabutylammonium fluoride in THF (5.0 mL, 5.0 mmol). The reaction is permitted to stir for 1 hour, at which time it is diluted with saturated aqueous NH4Cl and ethyl acetate. The layers are separated and the aqueous layer is extracted an additional two 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 (methanol-dichloromethane, 0:1 to 1:20) to furnish 3-(5-hydroxymethyl-imidazol-1-yl)-2,2-dimethyl-indan-1-one O-ethyl-oxime as a mixture of geometric isomers; HRMS: (ESI) m/z 300.1710 [(M+H)+: Calcd for C17H21N3O2: 300.1712]; ˜1:1.25 isomeric mixture. Major: 1H NMR (400 MHz, CDCl3) δ ppm 1.08 (s, 3 H), 1.32 (t, J=7.1 Hz, 3 H), 1.58 (s, 3 H), 4.20 (q, J=7.0 Hz, 2 H), 4.68-4.82 (m, 2 H), 5.59 (s, 1 H), 6.87-7.00 (m, 2 H), 7.17 (d, J=7.3 Hz, 1 H), 7.34-7.52 (m, 2 H), 7.71-7.79 (m, 1 H), Minor: 1H NMR (400 MHz, CDCl3) δ ppm 0.92 (s, 3 H), 1.38 (t, J=7.1 Hz, 3 H), 1.44 (s, 3 H), 4.27 (q, J=7.1 Hz, 2 H), 4.69-4.82 (m, 2 H), 5.60 (s, 1 H), 6.88-7.01 (m, 2 H), 7.28-7.30 (m, 1 H), 7.34-7.50 (m, 2 H), 8.37-8.45 (m, 1 H).

Workup

  1. temperatureThe reaction is then heated
  2. temperatureat reflux for 1 hour, at which time it
  3. concentrationconcentrated
  4. additionThe resulting residue is diluted with ethyl acetate
  5. washwashed with saturated aqueous NaHCO3
  6. dry with materialThe organic layer is dried with Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. dissolutionis dissolved in THF (30 mL)
  10. customThe layers are separated
  11. extractionthe aqueous layer is extracted an additional two times with ethyl acetate
  12. dry with materialThe combined organic layers are dried with Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe resulting residue is purified by silica gel flash chromatography (methanol-dichloromethane, 0:1 to 1:20)

Sources & evidence

ORD record
ord-6eb7b4c3ff894650941aefc18ae72780
Source dataset
uspto-grants-2013_05
Patent number
US08436035B2

Reaction notes

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