Reaction #838941

Reaction equation

hydrochloride

(S)-2-((S)-1-Benzyloxycarbonyl-ethylcarbamoyl)-piperidinium chloride

N-Boc-L-proline

HATU

ethyldiisopropylamine

ethyldiisopropylamine

→

tert-Butyl (S)-2-{1-[(S)-2-((S)-1-benzyloxycarbonyl-ethylcarbamoyl)-piperidin-1-yl]-methanoyl}-pyrrolidine-1-carboxylate

Solvents

methylene chloride

Conditions

Workup

1. 1
   workup.STIRRINGthe mixture is stirred at room temperature for 72 h
2. 2
   Otherevaporated
3. 3
   Washthe solution is washed with aq. citric acid and aq. sodium hydrogencarbonate solution and sat. aq. sodium chloride solution
4. 4
   Dryingdried over sodium sulfate
5. 5
   Otherevaporated
6. 6
   OtherThe residue is purified by means of silica gel chromatography
7. 7
   Other18.25 g (99% of th.) of product are obtained

Procedure

12.27 g (37.54 mmol) of the hydrochloride from example 21A and 10.50 g (48.81 mmol) of N-Boc-L-proline are dissolved in methylene chloride (30 ml) and cooled to 0° C. Subsequently, the solution is treated with 18.56 g (48.81 mmol) of HATU and 5.82 g (45.05 mmol) of ethyldiisopropylamine and stirred at 0° C. for 30 min. After further addition of 11.64 g (90.10 mmol) of ethyldiisopropylamine, the mixture is stirred at room temperature for 72 h and then evaporated. The residue is taken up using ethyl acetate and the solution is washed with aq. citric acid and aq. sodium hydrogencarbonate solution and sat. aq. sodium chloride solution, dried over sodium sulfate and evaporated. The residue is purified by means of silica gel chromatography using cyclohexane/ethyl acetate 5/1. 18.25 g (99% of th.) of product are obtained.

Source