Hydrochloric Acid → HCID 57781144, compound

HRID 1690764Notes

Reaction equation

HRID 1690764 reaction equation
O[CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5](=[O:12])[NH:4][C:3]1([CH3:14])[CH3:13].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:34][O:35][C:36]([C:38]1[N:39]=[CH:40][NH:41][CH:42]=1)=[O:37].N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.Cl.O1CCOCC1>C1COCC1.C(OCC)(=O)C.C([O-])(O)=O.[Na+]>[CH3:34][O:35][C:36]([C:38]1[N:39]([CH:2]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[O:12])[NH:4][C:3]2([CH3:14])[CH3:13])[CH:40]=[N:41][CH:42]=1)=[O:37]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 11776TriphenylphosphineHCID 312751,4-DioxaneHCID 97268Di-tert-butyl azodicarboxylateHCID 10655326HCID 10655326, compoundHCID 178418785HCID 178418785, compound

Product 1

HCID 57781144HCID 57781144, compound

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4-hydroxy-3,3-dimethyl-3,4-dihydro-2H-isoquinolin-1-one (1.15 g, 6.0 mmol) in THF (85 mL) is added triphenylphosphine (2.7 g, 10.2 mmol), and methyl-4-imidazolecarboxylate (1.3 g, 10.2 mmol). The heterogeneous reaction mixture is cooled to 0° C. and di-tert-butyl azodicarboxylate (2.4 g, 10.2 mmol) is added. The reaction is allowed to warm to room temperature and stirred for 45 min, and then heated at 40° C. for an additional 75 min, at which time the reaction is cooled to 0° C. and 4M HCl in dioxane (20 mL, 80 mmol) is added. The reaction is brought to room temperature and allowed to stir for 45 min. The reaction mixture is then basified to a pH of ca. 8 via the cautious addition of saturated aqueous NaHCO3. The resulting mixture is further diluted with ethyl acetate and saturated aqueous NaHCO3 and the layers are separated. The aqueous layer is extracted 3 times with ethyl acetate and the organic layers are combined, dried over Na2SO4, filtered and concentrated in vacuo. The resulting residue is adsorbed onto silica gel and submitted to silica gel flash chromatography [35 to 60% of a stock solution in hexanes (stock solution is made of 17% v/v reagent alcohol in ethyl acetate)] to provide 3-(3,3-dimethyl-1-oxo-1,2,3,4-tetrahydro-isoquinolin-4-yl)-3H-imidazole-4-carboxylic acid methyl ester as an off-white solid. HRMS (ESI) m/z 300.1354 [(M+H)+; calculated for C16H18N3O3: 340.1348]; 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.07 (s, 3 H), 1.45 (s, 3 H), 3.94 (s, 3 H), 5.72 (br. s., 11 H), 6.59 (s, 1 H), 7.32-7.38 (m, 1 H), 7.41 (s, 1 H), 7.50-7.61 (m, 2 H), 7.78 (s, 1 H), 8.19-8.28 (m, 1 H).

Workup

  1. temperatureto warm to room temperature
  2. temperatureheated at 40° C. for an additional 75 min, at which time the reaction
  3. temperatureis cooled to 0° C.
  4. customis brought to room temperature
  5. stirringto stir for 45 min
  6. customthe layers are separated
  7. extractionThe aqueous layer is extracted 3 times with ethyl acetate
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-763a027959e74f919658e79371aa033e
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

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