Triethylamine → tert-butyl 3-(1-benzyl-1H-pyrazol-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate

HRID 659637Notes

Reaction equation

HRID 659637 reaction equation
FC(F)(F)S(O[C:7]1[CH2:8][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][CH2:11][CH:12]=1)(=O)=O.[CH2:22]([N:29]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[N:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.C(N(CC)CC)C>C1(C)C=CC=CC=1.C(O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:22]([N:29]1[CH:33]=[C:32]([C:7]2[CH2:8][N:9]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH2:10][CH2:11][CH:12]=2)[CH:31]=[N:30]1)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 27347711-Benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 53978067tert-Butyl 3-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate

Product 1

HCID 67997011tert-butyl 3-(1-benzyl-1H-pyrazol-4-yl)-5,6-dihydropyridine-1(2H)-carboxylateYield 98%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolvent2×HCID 1140TolueneSolvent

Procedure

A 250-mL 3-necked round-bottomed flask was charged with a solution of tert-butyl 3-(trifluoromethylsulfonyloxy)-5,6-dihydropyridine-1(2H)-carboxylate (5.0 g, 15.11 mmol, 1.00 equiv) in toluene (100 mL), a solution of 1-benzyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (4.29 g, 15.11 mmol, 1.00 equiv) in ethanol (100 mL), triethylamine (4.58 g, 45.35 mmol, 3.00 equiv), Pd(PPh3)4 (345 mg, 0.30 mmol, 0.01 equiv) and water (30 mL). The resulting mixture was heated to reflux for 3 hours. Upon completion, the mixture was diluted with water (100 mL). Then, it was extracted with ethyl acetate (3×200 mL). Combined organic layers were dried over anhydrous sodium sulfate and concentrated on a rotary evaporator. The residue was purified by silica gel column chromatography eluted with ethyl acetate/petroleum ether (1:5) affording tert-butyl 3-(1-benzyl-1H-pyrazol-4-yl)-5,6-dihydropyridine-1(2H)-carboxylate as yellow oil (5.0 g, 98%).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureto reflux for 3 hours
  3. extractionThen, it was extracted with ethyl acetate (3×200 mL)
  4. dry with materialCombined organic layers were dried over anhydrous sodium sulfate
  5. concentrationconcentrated on a rotary evaporator
  6. customThe residue was purified by silica gel column chromatography
  7. washeluted with ethyl acetate/petroleum ether (1:5)

Sources & evidence

ORD record
ord-b8d32d5b00974c9288c4fc6f138fa45e
Source dataset
uspto-grants-2011_12
Patent number
US08080566B1

Reaction notes

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