Diisopropylethylamine → (R)-2-Amino-N-hydroxy-3-phenyl-propionamide

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Reaction Steps

To a solution of N-(9-fluorenylmethoxycarbonyl)-D-phenylalanine (2.09 g, 5.4 mmol) in dry dichloromethane/DMA 1:1 (20 ml) are added TPTU (1.76 g, 5.94 mmol) and N-ethyldiisopropylamine (1.02 ml, 5.94 mmol). After stirring for 5 min the mixture is added to aminooxy-2-chlorotrityl polystyrene resin (2.8 g, 2.7 mmol; Tetrahedron Lett. 1997, 38, 3311-3314) and the resulting suspension shaken at r.t. for 16 h. The mixture is filtered and the resin washed alternating with DMA and dichloromethane (3×). The described coupling procedure is repeated with a freshly prepared mixture of N-(9-fluorenylmethoxycarbonyl)-D-phenylalanine (2.09 g, 5.4 mmol), TPTU (1.76 g, 5.94 mmol) and N-ethyldiisopropylamine (1.02 ml, 5.94 mmol) in dichloromethane/DMA 1:1 (20 ml). After 16 h the suspension is filtered and the resin washed with DMA (2×), alternating with H2O and DMA (2×), alternating with 2-propanol and THF (3×), THF (2×) and dichloromethane (3×). The resin thus obtained is shaken for 30 min with a freshly prepared solution of dichloromethane/piperidine 8:2 (25 ml). After filtration, this process is repeated twice with fresh dichloromethane/piperidine solutions. The suspension is filtered, the resin washed with dichloromethane (2×), alternating with 2-propanol and dichloromethane (2×), dichloromethane (3×) and dried in vacuo, thus providing polymer-bound (R)-2-amino-N-hydroxy-3-phenyl-propionamide.

Provenance & Evidence