Methyl Acrylate → 1-(2-Methoxycarbonyl-ethyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester

HRID 967371Notes

Reaction equation

HRID 967371 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[NH:14][N:15]=[C:16]([C:17]3[CH:22]=[CH:21][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:19][CH:18]=3)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:27]([O:31][CH3:32])(=[O:30])[CH:28]=[CH2:29].C(O[Na])(C)(C)C>C1(C)C=CC=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]([CH2:29][CH2:28][C:27]([O:31][CH3:32])=[O:30])[N:15]=[C:16]([C:17]3[CH:18]=[CH:19][C:20]([C:23]([F:24])([F:25])[F:26])=[CH:21][CH:22]=3)[C:10]=2[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 7294Methyl AcrylateHCID 684638853-(4-Trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl esterHCID 178418730sodium 2-methylpropan-2-olate

Product 1

HCID 684627001-(2-Methoxycarbonyl-ethyl)-3-(4-trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl esterYield 15%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
75 °C

Procedure

3-(4-Trifluoromethyl-phenyl)-1,4,6,7-tetrahydro-pyrazolo[4,3-c]pyridine-5-carboxylic acid tert-butyl ester (1.85 g, 5.04 mmol) and methyl acrylate (0.50 mL, 5.6 mmol) were combined in toluene (30 mL) and heated to 75° C. The resulting mixture was treated with t-BuONa (100 mg), and heating continued for 48 h. The mixture was allowed to cool and partitioned between EtOAc (300 mL) and NaHCO3 (75 mL). The aqueous layer was extracted with EtOAc (3×75 mL). The combined extracts were dried over Na2SO4 and concentrated. Column chromatography (silica, 30-60% EtOAc/hexanes) afforded 343 mg (15%) of the title compound. TLC (silica, 50% EtOAc/hexanes): Rf=0.4. MS (electrospray): m/z calculated for C22H27F3N3O4 [M++H] 454.20. found 454.1. 1H NMR (CDCl3, 400 MHz): 7.75 (br d, J=8.1 Hz, 2H), 7.64 (br s, 2H), 4.63 (br s, 2H), 4.30 (t, J=6.6 Hz, 2H), 3.75 (br s, 2H), 3.68 (s, 3H), 2.98 (t, J=6.6 Hz, 2H), 2.79 (br t, J=5.6 Hz, 2H), 1.48 (s, 9H).

Workup

  1. temperatureheating
  2. temperatureto cool
  3. custompartitioned between EtOAc (300 mL) and NaHCO3 (75 mL)
  4. extractionThe aqueous layer was extracted with EtOAc (3×75 mL)
  5. dry with materialThe combined extracts were dried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-f3a7b1ef6eb54e0980b3f47062cd0128
Source dataset
uspto-grants-2005_10
Patent number
US06953793B2

Reaction notes

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