Sodium Carbonate → tert-Butyl 1-phenyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

HRID 548618Notes

Reaction equation

HRID 548618 reaction equation
C[N:2]([CH:4]=[C:5]1[C:10](=O)[CH2:9][CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6]1)C.C(=O)([O-])[O-].[Na+].[Na+].Cl.[C:26]1([NH:32]N)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C(=O)(O)[O-].[Na+]>CO.C(O)(=O)C.O>[C:26]1([N:32]2[C:10]3[CH2:9][CH2:8][N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][C:5]=3[CH:4]=[N:2]2)[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 60962Phenylhydrazine hydrochlorideHCID 516892Sodium BicarbonateHCID 53395404tert-butyl 3-[(dimethylamino)methylene]-4-oxotetrahydro-1(2H)-pyridinecarboxylate

Product 1

HCID 45789775tert-Butyl 1-phenyl-1,4,6,7-tetrahydro-5H-pyrazolo[4,3-c]pyridine-5-carboxylate

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Tert-butyl 3-((dimethylamino)methylene)-4-oxopiperidine-1-carboxylate (Step A, 2.1 g, 8.3 mmol) was dissolved in 100 mL methanol, and water (50 mL) was added followed by the addition of sodium carbonate (0.53 g, 5.0 mmol) and phenyl hydrazine hydrochloride (1.43 g, 9.9 mmol). Finally, acetic acid (1 mL) was added and the resulting mixture was stirred at rt for 1 h. The mixture was made basic by adding saturated aq. sodium bicarbonate (ca. 20 mL) and the methanol was removed on a rotary evaporator. The resulting mixture was extracted with methylene chloride (3×40 mL) and the combined extracts were dried over anhyd. sodium sulfate, filtered, and concentrated to afford the crude product. Purification by flash chromatography on silica gel using 20% ethyl acetate in hexanes as the eluant afforded fractions containing the desired product. Concentration of the combined fractions afforded the desired product b as a yellow oil (1.63 g, 66%). 1H NMR (400 MHz, d3-MeOD): δ 7.73 (s, 1H), 7.60-7.47 (m, 5H), 4.37 (s, 2H), 3.57 (t, J=6.1 Hz, 2H), 3.17 (t, J=6.0 Hz, 2H).

Workup

  1. customthe methanol was removed on a rotary evaporator
  2. extractionThe resulting mixture was extracted with methylene chloride (3×40 mL)
  3. customthe combined extracts were dried over anhyd
  4. filtrationsodium sulfate, filtered
  5. concentrationconcentrated
  6. customto afford the crude product
  7. customPurification by flash chromatography on silica gel using 20% ethyl acetate in hexanes as the eluant
  8. customafforded fractions

Sources & evidence

ORD record
ord-17aa282148ee4b29ba598dbf2c30674f
Source dataset
uspto-grants-2011_05
Patent number
US07943617B2

Reaction notes

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