1-Butanol → 2-(Dibutoxymethyl)-4-fluoro-1-nitrobenzene

HRID 2382578Notes

Reaction equation

HRID 2382578 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:10]([O-:12])=[O:11])=[C:6]([CH:9]=1)[CH:7]=[O:8].O.[C:14]1(C)[CH:19]=CC(S(O)(=O)=O)=[CH:16][CH:15]=1.[CH2:25]([OH:29])[CH2:26][CH2:27][CH3:28]>C1(C)C=CC=CC=1>[CH2:19]([O:8][CH:7]([O:29][CH2:25][CH2:26][CH2:27][CH3:28])[C:6]1[CH:9]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=1[N+:10]([O-:12])=[O:11])[CH2:14][CH2:15][CH3:16]

Participants

5

Reactant 3

HCID 2631-ButanolHCID 521998p-Toluenesulfonic acid monohydrateHCID 5870905-Fluoro-2-nitrobenzaldehyde

Product 1

HCID 112895602-(Dibutoxymethyl)-4-fluoro-1-nitrobenzene

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of 5-fluoro-2-nitrobenzaldehyde (75 g, 443 mmol), para-toluenesulfonic acid monohydrate (8.4 g, 44.3 mmol), and n-butanol (122 mL, 1.33 mol) was refluxed in toluene (630 mL) using a Dean-Stark apparatus for 15 h. The reaction was cooled, concentrated and partitioned between water (1 L) and EtOAc (1 L). The organic layer was washed with water (1 L) and brine (1 L), dried over Na2SO4 and concentrated. The crude reaction was purified by column chromatography (0 to 25% EtOAc in hexanes, 1% triethylamine buffer) to yield the 2-(dibutoxymethyl)-4-fluoro-1-nitrobenzene (A-1) as an oil. Data for A-1: 1HNMR (500 MHz, CDCl3) δ 7.92 (dd, J=8.5, 4.5 Hz, 1H), 7.54 (dd, J=9.0, 3.0 Hz, 1H), 7.15-7.11 (m, 1H), 6.05 (s, 1H), 3.67-3.52 (m, 4 H), 1.63-1.57 (m, 4 H), 1.43-1.35 (m, 4 H), 0.94-0.91 (m, 6 H) ppm; ESI MS [M+H] for C15H22FNO4 (-acetal)=169.8.

Workup

  1. customfor 15 h
  2. temperatureThe reaction was cooled
  3. concentrationconcentrated
  4. custompartitioned between water (1 L) and EtOAc (1 L)
  5. washThe organic layer was washed with water (1 L) and brine (1 L)
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe crude reaction
  9. customwas purified by column chromatography (0 to 25% EtOAc in hexanes, 1% triethylamine buffer)

Sources & evidence

ORD record
ord-bcbe46382c4147e4ae8c14f90a32f0aa
Source dataset
uspto-grants-2012_09
Patent number
US08263586B2

Reaction notes

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