Hydrochloric Acid → Methyl (S)-2-(Boc-amino)-4-iodobutanoate

Participants

Reaction Steps

To an ice cold suspension of (S)-methyl 2-amino-4-bromobutanoate, 1.00 HCl (see WO2003/101948 A2, 4.42 g, 19.02 mmol) and N,N-diisopropylethylamine (9.97 mL, 57.1 mmol) in anhydrous THF (50 mL) is slowly added a solution of di-tert-butyldicarbonate (4.36 g, 19.97 mmol) in anhydrous THF (8 mL). The reaction is stirred for 18 h while warming to room temp. The solvent is removed in vacuo, and the residue is partitioned between EtOAc (450 mL) and aqueous saturated ammonium chloride (30 ml). The organic layer is washed with aqueous saturated sodium bicarbonate (1×30 mL), water (1×30 mL), brine (1×30 mL), dried over Na2SO4, filtered and evaporated to dryness. The residue is dissolved in acetone (450 mL). treated with sodium iodide (14.25 g, 95.1 mmol) and the reaction is refluxed for 18 h. The reaction is cooled to room temp, filtered thru a ground glass frit and the solvent removed in vacuo. The residue is dissolved in EtOAc (450 mL), washed with water (3×40 mL), brine (1×40 mL), dried over Na2SO4, filtered, evaporated to dryness and purified by BIOTAGE® Silica gel chromatography on a 80 g Thompson Single Step silica cartridge using 100% CH2Cl2 over 10 column volumes to give 3.9 g (60%) of the title compound as a thick oil. LC/MS (Condition A): ret. T=3.40 min, (M+Na) 366.

Provenance & Evidence