1,2-Difluoro-4-nitrobenzene → HCID 16659476, compound

HRID 1350165Notes

Reaction equation

HRID 1350165 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[C:12](=[O:15])(O)[O-].[Na+]>C(O)C>[F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[NH:9][C@H:4]([CH2:3][CH3:2])[CH2:12][OH:15]

Participants

4

Reactant 2

HCID 1230531,2-Difluoro-4-nitrobenzene2×HCID 516892Sodium Bicarbonate

Product 1

HCID 16659476HCID 16659476, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of 118 g (0.74 mole) of 3,4-difluoronitrobenzene and 85 g (0.95 mole) of R-(+)-2-amino-1-butanol was dissolved in 400 mL of absolute ethanol. To this solution was then added 62.2 g (0.74 mole) of sodium bicarbonate. The suspension was stirred and heated at reflux temperature for 12 h when TLC indicated complete conversion of the 3,4-difluoronitrobenzene. After cooling to room temperature, the reaction mixture was filtered with the aid of additional ethanol and the ethanol was then evaporated. The crude product thus obtained was distilled under reduced pressure (10–112° C., 2 mm Hg) to afford (2R)-(+)-2-(2-fluoro-4-nitrophenyl)amino-1-butanol as a red solid. Yield, 162 g (96%). [α]D=+95.4 (CHCl3, c 22.7); 1H NMR (CDCl3) δ7.88 (1H, dd, J=2.4, 8.9), 7.76 (1H dd J=2.4, 11.7), 6.66 (1H, dd, J=8.7), 4.88 (1H, m), 3.76 (1H dd, J=4.2, 11.2), 3.68 (1H, dd J=4.2, 11.2), 3.52 (1H, m), 2.63 (1H, bs), 1.70 (1H, m), 1.59 (1H, m), 0.97 (3H, t, J=7.5). 13C NMR: ppm 150.1, 147.7, 142.8, 142.7, 136.1, 122.3, 110.9, 110.7, 109.5, 63.6, 55.8, 24.4, 10.4.

Workup

  1. temperatureheated
  2. temperatureat reflux temperature for 12 h when TLC
  3. filtrationthe reaction mixture was filtered with the aid of additional ethanol
  4. customthe ethanol was then evaporated
  5. customThe crude product thus obtained
  6. distillationwas distilled under reduced pressure (10–112° C., 2 mm Hg)

Sources & evidence

ORD record
ord-4defca78a9684d8fb75cc52a0c2ef8c5
Source dataset
uspto-grants-2007_05
Patent number
US07214690B2

Reaction notes

Loading…