Water → (R)-Methyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-2-hydroxy-2-phenylacetate

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The methyl(3RS)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (260 gm, 1.05 mol) (29) was charged in isopropanol (6.0 vol, 1.56 Ltr) at 25-30° C. and the reaction mixture was stirred for 15 minutes to give a clear solution. After 15 minutes stirring, controlled addition of a solution of (R)-(−)-mandelic acid [2.0 eq, 320 gm in 6.0 vol, 1.56 Ltr of isopropanol] was carried out. After completion of the addition, the reaction mixture was stirred at 25-30° C. for 3 hours to give enantiomerically enriched crude methyl(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-(−)-mandelate as a white coloured product. The product was filtered, washed with isopropanol (1.0 vol, 260 ml), and dried in a vacuum oven at 40-45° C. for 4-5 hours to give enantiomerically enriched crude methyl(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-(−)-mandelate (135 gm, molar yield: 64%). The dried enantiomerically enriched crude methyl(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-(−)-mandelate product (135 gm) was charged in isopropanol (20.0 vol, 2.7 Ltr) at 25-30° C. and the white suspension was further heated at 75-80° C. for 0.5 hour to give a partially clear solution. The partially clear solution was made clear by the addition of water (2.0 vol, 270.0 ml) at 75-80° C. The clear solution was further stirred for 0.5 hour. After stirring for 0.5 hour, the clear solution was gradually cooled to 0-5° C. within 3 hours to give enantiomerically enriched pure methyl(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-(−)-mandelate (30) as white coloured product. The product was filtered, washed with isopropanol (1.0 vol, 135.0 ml), and dried in a vacuum oven at 40-45° C. for 4-5 hours.

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