Dimethylformamide → 3-Formyl-1-(1-(2-pyridinyl)ethyl)pyrazole-5-carboxylic acid ethyl ester

HRID 129828Notes

Reaction equation

HRID 129828 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:10]=[C:9]([CH:11]=[O:12])[NH:8][N:7]=1)=[O:5])[CH3:2].CN(C)C=O.[H-].[Na+].Br[CH:21]([C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=1)[CH3:22]>O>[CH2:1]([O:3][C:4]([C:6]1[N:7]([CH:21]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[CH3:22])[N:8]=[C:9]([CH:11]=[O:12])[CH:10]=1)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 3542775Ethyl 5-formyl-1H-pyrazole-3-carboxylateHCID 153736572-(1-Bromoethyl)pyridine

Product 1

HCID 152969373-Formyl-1-(1-(2-pyridinyl)ethyl)pyrazole-5-carboxylic acid ethyl esterYield 45.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a mixture of 5-formylpyrazole-3-carboxylic acid ethyl ester (5.42 g) and anhydrous dimethyl formamide (80 ml), 1.41 g of 60% sodium hydride oil suspension were added at 0° C. After 30 minutes, 6.30 g of 2-(1-bromoethyl)pyridine were added at 0° C. The mixture was stirred overnight at room temperature and 120 ml of water was added thereto. The mixture was extracted with ethyl acetate (3×300 ml). The combined organic solution was dried over sodium sulfate and concentrated. The residue was chromatographed (silica gel, Hex/EtOAc 2/1) to afford 4.0 g of 3-formyl-1-(1-(2-pyridinyl)ethyl)pyrazole-5-carboxylic acid ethyl ester as a viscous oil. NMR: 1.33 (t, 3H), 2.01 (d, 3H), 4.29 (m, 2H), 6.73 (q, 1H), 7.40 (s, 1H, 4-pyrazolyl H) 7.06, 7.19, 7.63, 8.57 (4 m, 4H, pyridyl H's), 10.04 (s, 1H, CHO). Also obtained was 535 mg of 5-formyl-1-(1-(2-pyridyl)ethyl)pyrazole-3-carboxylic acid ethyl ester as a viscous oil. NMR: 1.41 (t, 3H), 2.05 (d, 3H), 4.42 (q, 2H), 5.51 (q, 1H), 7.46 (s, 1H, 4-pyrazolyl H), 7.07, 7.17, 7.61, 8.54 (4 m, 4H, pyridyl H's), 9.88 (s, 1H, CHO).

Workup

  1. additionwere added at 0° C
  2. extractionThe mixture was extracted with ethyl acetate (3×300 ml)
  3. dry with materialThe combined organic solution was dried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was chromatographed (silica gel, Hex/EtOAc 2/1)

Sources & evidence

ORD record
ord-42645b34e83545439fd903ca5ed20a82
Source dataset
uspto-grants-1995_11
Patent number
US05470862

Reaction notes

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