Hydrochloric Acid → 2-(2-Fluoro-6-nitrophenyl)ethan-1-ol

HRID 620919Notes

Reaction equation

HRID 620919 reaction equation
[OH-:1].[K+].[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-:12])=[O:11])[C:5]=1[CH3:13].[CH2:14]=O.Cl>C(O)C.CS(C)=O.O>[F:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([N+:10]([O-:12])=[O:11])[C:5]=1[CH2:13][CH2:14][OH:1]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 712FormaldehydeHCID 14797Potassium HydroxideHCID 698542-Fluoro-6-nitrotoluene

Product 1

HCID 156914472-(2-Fluoro-6-nitrophenyl)ethan-1-ol

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 702EthanolSolventHCID 962WaterSolvent

Procedure

According to the procedure of L. Florvall et al. J. Med. Chem. 29, 1406 (1986), a solution of KOH (0.75 g) in ethanol (5 mL) was added to a mixture of 2-fluoro-6-nitrotoluene (77.5 g, 0.5 mole) and paraformaldehyde (15 g, 0.5 mole) in DMSO (75 mL). The dark solution was stirred for 3 days at room temperature, diluted with water (1.2 L), neutralized with 2.5N HCl (to pH 6.5) and extracted with ether (3×). The extracts were washed with brine (1×), dried (MgSO4) and evaporated to dryness to yield a yellow solid. Trituration with light petroleum ether removed a small amount of unreacted starting material and provided 2-fluoro-6-nitrophenethyl alcohol as a pale yellow solid, 82.3 g, 89.3%, m.p. 42°-44° C. This material was used for the subsequent reaction without further purification. An analytical sample was purified by flash chromatography (silica Merck-60, hexane-ether 6:4), m.p. 45°-46° C.

Workup

  1. extractionextracted with ether (3×)
  2. washThe extracts were washed with brine (1×)
  3. dry with materialdried (MgSO4)
  4. customevaporated to dryness
  5. customto yield a yellow solid
  6. customTrituration with light petroleum ether removed a small amount

Sources & evidence

ORD record
ord-635a99feb98940b2a8fd69654698af46
Source dataset
uspto-grants-1989_04
Patent number
US04822893

Reaction notes

Loading…