Tetrahydrofuran → Ethyl 5-butylamino-1-methylpyrazole-4-carboxylate

HRID 1728346Notes

Reaction equation

HRID 1728346 reaction equation
[NH2:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].O1[CH2:27][CH2:26][CH2:25][CH2:24]1.ICCCC>CN(C)C=O.C(=O)(O)[O-].[Na+]>[CH2:24]([NH:1][C:2]1[N:6]([CH3:7])[N:5]=[CH:4][C:3]=1[C:8]([O:10][CH2:11][CH3:12])=[O:9])[CH2:25][CH2:26][CH3:27]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 10962Butyl iodideHCID 271299Ethyl 5-amino-1-methyl-1H-pyrazole-4-carboxylateHCID 2724254Sodium bis(trimethylsilyl)amide

Product 1

HCID 19017701Ethyl 5-butylamino-1-methylpyrazole-4-carboxylateYield 84.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To ethyl 5-amino-1-methylpyrazole-4-carboxylate (3.4476 g, 20.38 mmol) in dimethylformamide (60 mL) at 0° C. was added a solution of 1.0M sodium bis(trimethylsilyl)amide in tetrahydrofuran (20.5 mL, 20.5 mmol). After 1 hour, 1-iodobutane (2.50 mL, 22.0 mmol) was added and the reaction was stirred at ambient temperature for 20 hours. The mixture was diluted with saturated aqueous sodium bicarbonate and extracted with ethyl acetate (6×). The combined organic extracts were then washed with water (2×) and brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. Chromatography of the residue on silica gel eluting with 20% ethyl acetate in hexane afforded 3.8754 g (84%) of the desired product as a oil. TLC (20% ethyl acetate/80% hexane) Rf =0.12. 1H NMR (CDCl3, 300 MHz) d 0.94 (t, 3H), 1.33 (t, 3H), 1.35-1.50 (m, 2 H), 1.53-1.65 (m, 2H), 3.25 (t, 2H), 3.77 (s, 3H), 4.25 (q, 2H), 5.60-5.80 (br, 1H), 7.62 (s, 1H). MS (DCl/NH3)m/e 226 (M+H)+.

Workup

  1. extractionextracted with ethyl acetate (6×)
  2. washThe combined organic extracts were then washed with water (2×) and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-0ac50d78f17b4f3596de7aff1ac88ce2
Source dataset
uspto-grants-1994_07
Patent number
US05326776

Reaction notes

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