Tetrahydrofuran → 5-Benzyl 3-methyl 1-(p-fluorophenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylate

HRID 268632Notes

Reaction equation

HRID 268632 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:9]([CH:10]([CH3:12])[CH3:11])[CH:8]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[N:7]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[N:6]=1)=[O:4].C1COCC1>C1COCC1.O>[CH3:1][O:2][C:3]([C:5]1[C:9]([CH:10]([CH3:12])[CH3:11])=[C:8]([C:13]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)=[O:14])[N:7]([C:23]2[CH:28]=[CH:27][C:26]([F:29])=[CH:25][CH:24]=2)[N:6]=1)=[O:4]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 598319971-(4-fluoro-phenyl)-4-isopropyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylic acid 5-benzyl ester 3-methyl ester

Product 1

HCID 247549715-Benzyl 3-methyl 1-(p-fluorophenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylateYield 65%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a solution of 1-(4-fluoro-phenyl)-4-isopropyl-4,5-dihydro-1H-pyrazole-3,5-dicarboxylic acid 5-benzyl ester 3-methyl ester (29.3, 73.5 mmol) in THF:Water (1:1, 500 mL) at 0° C. was slowly added ceric ammonium nitrate (80.5 g, 147 mmol; commercially available from Sigma Aldrich). The reaction was stirred at 0° C. for 1 hr after which time the THF was removed under reduced pressure and DCM (500 mL) was added. The organic layer was separated and washed with water and brine. The organic layer was dried over Na2SO4 and concentrated, and the product was purified by silica gel chromatography (5-15% EtOAc/Hex) to provide 1-(4-fluoro-phenyl)-4-isopropyl-1H-pyrazole-3,5-dicarboxylic acid 5-benzyl ester 3-methyl ester (18.95 g, 65%):: H-NMR (CDCl3) δ 7.29-7.21 (m, 5 H), 7.07 (d, 2 H), 6.94 (t, 2 H), 5.12 (s, 2 H), 3.89 (s, 3 H), 3.88-3.80 (m, 1 H), 1.31 (d, 6 H).

Workup

  1. customat 0° C.
  2. customwas removed under reduced pressure and DCM (500 mL)
  3. additionwas added
  4. customThe organic layer was separated
  5. washwashed with water and brine
  6. dry with materialThe organic layer was dried over Na2SO4
  7. concentrationconcentrated
  8. customthe product was purified by silica gel chromatography (5-15% EtOAc/Hex)

Sources & evidence

ORD record
ord-a784ff0d50404bb296311273f7807fcc
Source dataset
uspto-grants-2008_11
Patent number
US07446121B2

Reaction notes

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