Pyridine → HCID 67566648, compound

HRID 1182308Notes

Reaction equation

HRID 1182308 reaction equation
[CH3:1][C:2]([CH3:22])([CH3:21])[C@H:3]([OH:20])[CH2:4][N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[CH:8][CH:7]=[N:6]1.Cl[C:24]([O:26][C:27]1[CH:32]=[CH:31][C:30]([N+:33]([O-:35])=[O:34])=[CH:29][CH:28]=1)=[O:25].N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>ClCCCl>[C:24](=[O:25])([O:20][C@H:3]([CH2:4][N:5]1[C:9]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[CH:8][CH:7]=[N:6]1)[C:2]([CH3:22])([CH3:21])[CH3:1])[O:26][C:27]1[CH:28]=[CH:29][C:30]([N+:33]([O-:35])=[O:34])=[CH:31][CH:32]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 821294-Nitrophenyl chloroformateHCID 516892Sodium BicarbonateHCID 69512321HCID 69512321, compound

Product 1

HCID 67566648HCID 67566648, compoundYield 91%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To 562.0 mg (1.80 mmol) of (2S)-3,3-dimethyl-1-{5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}-2-butanol in 18 mL of 1,2-dichloroethane at room temperature was added 544.1 mg (2.70 mmol) of 4-nitrophenyl chloroformate. Then, 291.1 μL (3.60 mmol) of pyridine was added, and the solution was heated at reflux for 16 h. Saturated aqueous sodium bicarbonate was added, and the resulting mixture was extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate, filtered, and concentrated. The residue was purified by silica gel column chromatography eluting with an ethyl acetate:hexanes solution (3:7) to give 779.7 mg (91%) of 4-nitrophenyl (1S)-2,2-dimethyl-1-({5-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl carbonate. Rf=0.21 (3:7 ethyl acetate:hexanes); 1H-NMR (300 MHz, DMSO-d6): δ 8.29 (d, J=8 Hz, 2H), 7.87 (d, J=8 Hz, 2H), 7.73 (d, J=8 Hz, 2H), 7.63 (s, 1H), 7.33 (d, J=9 Hz, 2H), 6.52 (s, 1H), 4.71 (d, J=9 Hz, 1H), 4.64 (d, J=15 Hz, 1H), 4.33 (dd, J=15 Hz, J=10 Hz, 1H), 0.89 (s, 9H); ES-LCMS m/z 478 (M+H).

Workup

  1. temperaturethe solution was heated
  2. temperatureat reflux for 16 h
  3. extractionthe resulting mixture was extracted with ethyl acetate
  4. dry with materialThe extract was dried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by silica gel column chromatography
  8. washeluting with an ethyl acetate

Sources & evidence

ORD record
ord-126e924bbd074fc0bf9c7f69a9d32e0c
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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