Dichloromethane → 4-Methylmorpholine

Participants

Reaction Steps

A suspension of 1.500 g (5.04 mmoles) of N-benzyloxycarbonyl-(S)-(-)-indoline-2-carboxylic acid (abbreviation Z-(S)-DhioH, prepared from (S)-(-)-indoline-2-carboxylic acid (Aldrich) according to the method of Wunsch [E. Wunsch, W. Graf, O. Keller, W, Keller, G. Wersin: Synthesis, (11), 958 (1986)]) in 80 ml of dry methylene chloride (CH2Cl2) was brought under argon atmosphere to a temperature of approximately -20° C. On stabilization of the temperature, the following were added in quick succession: 0.680 ml (5.20 mmoles) of isobutylchloroformate (IBCF) and 0.580 ml (5.26 mmoles) of 4-methylmorpholine (NMM), leaving the system under stirring for approximately 2 minutes. A solution, precooled to approximately -15° C. for 30 minutes, of 1.840 g (5.00 mmoles) of (L)-Leu-(L)-TrpOMe.HCl (Novabiochem) and 0.560 ml (5.08 mmoles) of NMM in 25 ml of anhydrous N,N-dimethylformamide (DMF) was then added, leaving, under stirring and static argon, the temperature of the bath free to rise to room temperature. After approximately 5 hours of reaction, the white precipitate was then filtered away and washed with a little CH2 Cl2. The latter was put back into the pale yellow coloured organic solution, which was extracted in succession using 5% NaHCO3 (3×30 ml); saturated aqueous NaCl (2×30 ml); 4% KHSO4 (3×30 ml) and finally saturated aqueous NaCl (3×30 ml), discarding the aqueous phases. The organic phase extracted, of a pale yellow colour, was left in a cold chamber under argon and on anhydrous Na2SO4 for 12 hours. The desiccant was then filtered away and the organic solution, concentrated to a small volume, was added dropwise under stirring to 200 ml of dry petroleum ether (30/50), obtaining an abundant white precipitate which, after several hours at rest in a cold chamber, was filtered, discarding the organic solution. The residual solid was left for 24 hours under vacuum on P2O5. 2.440 g (79.9%) of an analytically pure white solid were recovered.

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