Reaction #57289

Reaction equation

2-methoxyethoxymethyl chloride

5-hydroxy-2-nitrobenzaldehyde

tetrahydrofuran

N,N-diisopropylethylamine

→

2

Yield 97.0%

5-(2-methoxy-ethoxymethoxy)-2-nitro-benzaldehyde

Yield 97.0%

Solvents

dichloromethane

Conditions

Workup

1. 1
   Otherthe resulting reaction mixture
2. 2
   workup.STIRRINGstirred for 10 minutes at 0° C.
3. 3
   Temperaturewarmed up to room temperature
4. 4
   workup.STIRRINGto stir at room temperature for 18 hours
5. 5
   ConcentrationThe reaction mixture was concentrated under reduced pressure, and 150 mL of ethyl acetate
6. 6
   workup.ADDITIONwere added
7. 7
   FiltrationThe resulting off-white precipitate was filtered off
8. 8
   Otherthe filtrate was transferred into a separatory funnel
9. 9
   WashThe organic layer was washed with 75 mL of 1N sodium hydroxide solution, 100 mL water, and 75 mL brine
10. 10
    DryingThe organic layer was dried over anhydrous potassium carbonate
11. 11
    Filtrationfiltered
12. 12
    Concentrationconcentrated

Procedure

A suspension of 5 g (30 mmol) of 5-hydroxy-2-nitrobenzaldehyde (1) in 100 mL of dichloromethane and 10 mL of freshly distilled tetrahydrofuran was cooled to 0° C. To this suspension 6.25 mL (57 mmol) of N,N-diisopropylethylamine was added, and the resulting reaction mixture was stirred for 5 minutes. To this reaction mixture 3.76 mL (33 mmol) of 2-methoxyethoxymethyl chloride was added, stirred for 10 minutes at 0° C., warmed up to room temperature, and allowed to stir at room temperature for 18 hours. The reaction mixture was concentrated under reduced pressure, and 150 mL of ethyl acetate were added. The resulting off-white precipitate was filtered off, and the filtrate was transferred into a separatory funnel. The organic layer was washed with 75 mL of 1N sodium hydroxide solution, 100 mL water, and 75 mL brine. The organic layer was dried over anhydrous potassium carbonate, filtered, and concentrated to give 7.4 g (29 mmol, 97%) of 2 [LC-MS; M+Na 278].

Source