Formaldehyde → 2-(2-Fluoro-6-nitrophenyl)ethan-1-ol

HRID 963752Notes

Reaction equation

HRID 963752 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[CH3:11].[CH2:12]=[O:13]>C(O)(C)(C)C.CS(C)=O>[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([N+:8]([O-:10])=[O:9])[C:3]=1[CH2:11][CH2:12][OH:13]

Participants

5

Reactant 2

HCID 712FormaldehydeHCID 698542-Fluoro-6-nitrotoluene

Product 1

HCID 156914472-(2-Fluoro-6-nitrophenyl)ethan-1-olYield 71%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6386tert-ButanolSolvent

Conditions

Temperature
70 °C

Procedure

A solution of potassium tertiary-butylate (90 mg, 0.8 mmol) in tert.-butanol (1 ml, synthesis quality, 99%) was added to 2-fluoro-6-nitrotoluene (776 mg, 5 mmol) and paraformaldehyde (150 mg, 5 mmol) in DMSO (2.5 ml, synthesis quality, additionally dried for 2 d over molecular sieve 4 Å). After the addition of the potassium tertiary-butylate solution, a color change from yellow to deep violet occurred. The solution was stirred for 5 min at room temperature and for 30 min at 70° C. (oil bath temperature). It was then left to cool down to room temperature and neutralized with a few drops of conc. HCl. The mixture was diluted with EtOAc (30 ml) and washed with H2O (20 ml). The aqueous phase was post-extracted with EtOAc (2×20 ml). Drying the organic phases over Na2SO4, filtering and evaporating the solvent under reduced pressure yielded the crude product (1.11 g) which was purified by column chromatography (20 g SiO2, 12×2 cm, solvent: PE 40 ml, PE/EtOAc 10:1 110 ml, 8:1 270 ml, 6:1 210 ml, 5:1 60 ml, 4:1 50 ml). 2-(2-fluoro-6-nitrophenyl)ethanol (653 mg, 71%) was obtained as a yellow solid.

Workup

  1. custom2.5 ml, synthesis quality
  2. customadditionally dried for 2 d over molecular sieve 4 Å)
  3. additionAfter the addition of the potassium tertiary-butylate solution
  4. waitIt was then left
  5. temperatureto cool down to room temperature and neutralized with a few drops of conc. HCl
  6. additionThe mixture was diluted with EtOAc (30 ml)
  7. washwashed with H2O (20 ml)
  8. extractionThe aqueous phase was post-extracted with EtOAc (2×20 ml)
  9. dry with materialDrying the organic phases over Na2SO4
  10. filtrationfiltering
  11. customevaporating the solvent under reduced pressure
  12. customyielded the crude product (1.11 g) which
  13. customwas purified by column chromatography (20 g SiO2, 12×2 cm, solvent: PE 40 ml, PE/EtOAc 10:1 110 ml, 8:1 270 ml, 6:1 210 ml, 5:1 60 ml, 4:1 50 ml)

Sources & evidence

ORD record
ord-0328e02a8d31430fb418624df273358d
Source dataset
uspto-grants-1998_06
Patent number
US05763599

Reaction notes

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