Reaction #1283

Reaction equation

sodium hydride

1-fluoro-2-nitrobenzene

methylene chloride

N-[(1,1-dimethylethoxy)carbonyl]-L-serine

→

N-[(1,1-Dimethylethoxy)carbonyl]-O-(2-nitrophenyl)-L-serine

Solvents

methanol

dimethylformamide

acetic acid

dimethylformamide

Conditions

Workup

1. 1
   Temperaturea cooled
2. 2
   Otherwas continued at 0° until the frothing
3. 3
   Other(about 2.0 hours)
4. 4
   workup.STIRRINGstirred at 0° under argon for 4.0 hours
5. 5
   Extractionextracted with ethyl acetate (2×100 ml.)
6. 6
   Extractionextracted with ethyl acetate (3×500 ml.)
7. 7
   Washthe combined organic extracts were washed with brine (100 ml.)
8. 8
   Dryingdried (anhydrous sodium sulfate)
9. 9
   Filtrationfiltered
10. 10
    Otherevaporated to dryness
11. 11
    Otherdried in vacuo
12. 12
    OtherThe crude product mixture was chromatographed on a silica gel column (Merck)
13. 13
    Washeluting the column with methylene chloride:methanol:acetic acid (100:5:0.2)
14. 14
    Otherto give 27.22 g

Procedure

A solution of N-[(1,1-dimethylethoxy)carbonyl]-L-serine (24.3 g., 0.118 mole) in dry dimethylformamide (25 ml.) was added dropwise over a period of 1.0 hour to a cooled (0°, ice-salt bath) suspension of 60% sodium hydride (10.1 g., 0.25 mole) in dry dimethylformamide (200 ml.) and stirring was continued at 0° until the frothing subsided (about 2.0 hours). The reaction mixture was treated dropwise with 1-fluoro-2-nitrobenzene (14.3 ml., 0.13 mole) over a period of 20 minutes, stirred at 0° under argon for 4.0 hours then poured into ice-water (750 ml.) and extracted with ethyl acetate (2×100 ml.). The aqueous phase was brought to pH 1.0 with 6N hydrochloric acid (70 ml.), extracted with ethyl acetate (3×500 ml.) and the combined organic extracts were washed with brine (100 ml.), dried (anhydrous sodium sulfate), filtered, evaporated to dryness and dried in vacuo. The crude product mixture was chromatographed on a silica gel column (Merck), eluting the column with methylene chloride:methanol:acetic acid (100:5:0.2) to give 27.22 g. of product as a thick yellow syrup; Rf =0.27 (methylene chloride:methanol:acetic acid, 100:5:0.5).

Source