4-Nitrophenyl chloroformate → HCID 69512152, compound

HRID 1182307Notes

Reaction equation

HRID 1182307 reaction equation
[CH3:1][C:2]([CH3:22])([CH3:21])[C@H:3]([OH:20])[CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[CH:7]=[N:6]1.C([Li])CCC.Cl[C:29]([O:31][C:32]1[CH:37]=[CH:36][C:35]([N+:38]([O-:40])=[O:39])=[CH:34][CH:33]=1)=[O:30].C(=O)(O)[O-].[Na+]>O1CCCC1>[C:29](=[O:30])([O:31][C:32]1[CH:33]=[CH:34][C:35]([N+:38]([O-:40])=[O:39])=[CH:36][CH:37]=1)[O:20][C@H:3]([CH2:4][N:5]1[CH:9]=[C:8]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[CH:7]=[N:6]1)[C:2]([CH3:22])([CH3:21])[CH3:1]

Participants

6

Reactant 4

HCID 821294-Nitrophenyl chloroformateHCID 516892Sodium BicarbonateHCID 69512788HCID 69512788, compoundHCID 178418339Butyllithium

Product 1

HCID 69512152HCID 69512152, compoundYield 78%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 3.30 g (10.57 mmol) of (2S)-3,3-dimethyl-1-{4-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}-2-butanol in 200 mL of tetrahydrofuran at 0° C. was added 7.26 mL (11.62 mmol) of 1.6 M n-butyllithium in hexanes, and the resulting solution was stirred for 10 min. Then, 3.19 g (15.84 mmol) of 4-nitrophenyl chloroformate in 11 mL of tetrahydrofuran was added, and the solution was stirred at room temperature for 75 min. Saturated aqueous sodium bicarbonate was added, and the resulting mixture was extracted with ethyl acetate. The extract was washed with saturated aqueous sodium chloride, 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 3.92 g (78%) of (1S)-2,2-dimethyl-1-({4-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-yl}methyl)propyl 4-nitrophenyl carbonate. Rf=0.19 (3:7 ethyl acetate:hexanes); 1H-NMR (300 MHz, DMSO-d6): δ 8.44 (s, 1H), 8.14 (d, J=9 Hz, 2H), 8.08 (s, 1H), 7.79 (d, J=8 Hz, 2H), 7.70 (d, J=8 Hz, 2H), 7.27 (d, J=9 Hz, 2H), 4.88 (dd, J=10 Hz, J=2 Hz, 1H), 4.61 (d, J=13 Hz, 1H), 4.32 (dd, J=15 Hz, J=10 Hz, 1H), 1.05 (s, 9H); ES-LCMS m/z 478 (M+H).

Workup

  1. stirringthe solution was stirred at room temperature for 75 min
  2. extractionthe resulting mixture was extracted with ethyl acetate
  3. washThe extract was washed with saturated aqueous sodium chloride
  4. dry with materialdried 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-1f84e9ef8759484fa07fcd8454060c33
Source dataset
uspto-grants-2007_10
Patent number
US07288541B2

Reaction notes

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