Reaction #362831

Reaction equation

(S)-N-tert-butoxycarbonyltyrosine

sodium hydride

sodium hydride

1-tosyl-2-chloroethanol

1-tosyl-2-chloroethanol

→

(S)-N-tert-butoxycarbonyl-4-O-(2-chloroethyl)tyrosine

Yield 79.0%

Solvents

water

water

DMF

Conditions

Workup

1. 1
   Otherare placed in a three-necked flask under a nitrogen atmosphere
2. 2
   workup.STIRRINGhas been stirred for 2 days
3. 3
   workup.WAITThe same procedure is carried out after 24 h
4. 4
   workup.WAITthe stirring is continued for a further 24 h
5. 5
   Concentrationthe reaction mixture is concentrated to dryness under reduced pressure
6. 6
   OtherThe residue which is obtained
7. 7
   Extractionextracted with 3 times 100 ml of ethyl acetate
8. 8
   OtherThe aqueous phase is separated off
9. 9
   Extractionthe product is extracted with 3 times 100 ml of ethyl acetate
10. 10
    Washwashed with 2 times 50 ml of water
11. 11
    Otherseparated off
12. 12
    Dryingdried over magnesium sulphate
13. 13
    Filtrationfiltered
14. 14
    Concentrationconcentrated to dryness under reduced pressure in order

Procedure

14 g of (S)-N-tert-butoxycarbonyltyrosine, dissolved in 140 ml of DMF, are placed in a three-necked flask under a nitrogen atmosphere. 4.8 g of 50% sodium hydride in oil are added slowly using a spatula. 16.87 g of 1-tosyl-2-chloroethanol are added after the mixture has been stirred for 2 h at room temperature. 2.4 g of 50% sodium hydride in oil, and a further 8.4 ml of 1-tosyl-2-chloroethanol, are added after the mixture has been stirred for 2 days. The same procedure is carried out after 24 h and the stirring is continued for a further 24 h. The reaction is stopped by adding 100 ml of distilled water, and the reaction mixture is concentrated to dryness under reduced pressure. The residue which is obtained is taken up in 100 ml of distilled water and then extracted with 3 times 100 ml of ethyl acetate. The aqueous phase is separated off after settling and acidified to pH3 with 50 ml of 1N HCl, and the product is extracted with 3 times 100 ml of ethyl acetate. The organic phases are combined, washed with 2 times 50 ml of water, separated off, dried over magnesium sulphate, filtered and then concentrated to dryness under reduced pressure in order to yield 13.51 g of (S)-N-tert-butoxycarbonyl-4-O-(2-chloroethyl)tyrosine in the form of a chestnut oil (Rf=0.5, toluene 70%/methanol 20%/diethylamine 10%), which is used as such in the following step.

Source