Benzyl Alcohol → 1-(3-(Benzyloxy)-2-fluoro-6-nitrophenyl)propan-2-one

HRID 1163048Notes

Reaction equation

HRID 1163048 reaction equation
[F:1][C:2]1[C:7](F)=[CH:6][CH:5]=[C:4]([N+:9]([O-:11])=[O:10])[C:3]=1[CH2:12][C:13](=[O:15])[CH3:14].[CH2:16]([OH:23])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.O[Li].O.Cl>ClCCl>[CH2:16]([O:23][C:7]1[C:2]([F:1])=[C:3]([CH2:12][C:13](=[O:15])[CH3:14])[C:4]([N+:9]([O-:11])=[O:10])=[CH:5][CH:6]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1

Participants

6

Reactant 4

HCID 244Benzyl AlcoholHCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 142688761-(2,3-Difluoro-6-nitrophenyl)propan-2-one

Product 1

HCID 112896631-(3-(Benzyloxy)-2-fluoro-6-nitrophenyl)propan-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
105 °C

Procedure

To a solution of 1-(2,3-difluoro-6-nitrophenyl)-propan-2-one (2.5 g, 82% purity by HPLC analysis, 9.54 mmol) were added benzyl alcohol (2.5 mL) and LiOH.H2O (1.07 g, 25.58 mmol). The reaction mixture was then heated to 100-110° C. and stirred for 4 hours until HPLC analysis indicated complete reaction. After cooling to RT, the reaction mixture was diluted with dichloromethane (18 mL) and neutralized to pH 6-7 with 1 N HCl. The layers were separated and the organic phase was washed with brine and collected. With stirring, heptane (30-25 mL) was added to the organic solution whereupon crystallization was initiated. The resulting slurry was cooled to 0-5° C. and stirred for an additional 1 h. The slurry was then filtered and the filter cake was washed with heptane. The yellow-brown solids were then dried in vacuo at 50° C. for 12-15 h to afford 1.6 g of the desired compound which was 95% pure by HPLC analysis. HPLC method: Column: YMC Pack Cyano 3 um 4.6×50 mm Solvent A: 0.05% TFA in MeOH:Water (20:80), Solvent B: 0.05% TFA in MeOH:water (20:80), Wavelength: 254 nm Flow Rate: 3 mL/min. Gradient Time: 3 min. Final % B: 100 Initial Hold: 0.5 min. Start % B: 0. Typical Retention Times: SM, 1.2 min; Product 2.2-2.3 min.

Workup

  1. customreaction
  2. temperatureAfter cooling to RT
  3. customThe layers were separated
  4. washthe organic phase was washed with brine
  5. customcollected
  6. stirringWith stirring
  7. additionheptane (30-25 mL) was added to the organic solution whereupon crystallization
  8. temperatureThe resulting slurry was cooled to 0-5° C.
  9. stirringstirred for an additional 1 h
  10. filtrationThe slurry was then filtered
  11. washthe filter cake was washed with heptane
  12. customThe yellow-brown solids were then dried in vacuo at 50° C. for 12-15 h

Sources & evidence

ORD record
ord-7e1863b8820b45b7a16a7bbbb334c8e0
Source dataset
uspto-grants-2010_10
Patent number
US07820814B2

Reaction notes

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