Benzyl chloroformate → 2,6-Difluoro-3-nitro-benzoic acid benzyl ester

HRID 1187293Notes

Reaction equation

HRID 1187293 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N+:9]([O-:11])=[O:10].Cl[C:13]([O:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:14].C(NC(C)C)(C)C.[Li]>O1CCCC1>[CH2:16]([O:15][C:13](=[O:14])[C:7]1[C:6]([F:8])=[CH:5][CH:4]=[C:3]([N+:9]([O-:11])=[O:10])[C:2]=1[F:1])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

5

Reactant 3

HCID 10387Benzyl chloroformateHCID 679672,4-DifluoronitrobenzeneHCID 45051747Lithium diisopropylamine

Product 1

HCID 583170052,6-Difluoro-3-nitro-benzoic acid benzyl esterYield 2.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2,4-Difluoro-1-nitro-benzene (46, 1.4 mL, 13.0 mmol) and benzyl chloroformate (31, 10.42 g, 61.1 mmol) in 20 mL of tetrahydrofuran is cooled to −78° C. and stirred for 1 hour. Lithium diisopropylamine (1.5 g, 14.0 mmol) is added dropwise and the reaction is stirred at −78° C. for 1 hour, then warmed to room temperature over 2 hours. The reaction was purified by silica gel chromatography, eluting with hexane:ethyl acetate 90:10. Appropriate fractions are combined and concentrated under vacuum, then washed with methanol and the solid collected by filtration to provide the desired compound (47, 110 mg).

Workup

  1. stirringthe reaction is stirred at −78° C. for 1 hour
  2. customThe reaction was purified by silica gel chromatography
  3. washeluting with hexane:ethyl acetate 90:10
  4. concentrationconcentrated under vacuum
  5. washwashed with methanol
  6. filtrationthe solid collected by filtration

Sources & evidence

ORD record
ord-e3d7537d5e3b4be284b7f3a26ff19fc7
Source dataset
uspto-grants-2014_03
Patent number
US08673928B2

Reaction notes

Loading…