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

HRID 84152

反応式

HRID 84152 の反応式
[NH2:1][CH:2]([CH2:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[F:17])[CH2:3][C:4]([O:6][CH3:7])=[O:5].[C:18]([OH:28])(=[O:27])[C@@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[OH:20].O>C(O)(C)C>[C:18]([OH:28])(=[O:27])[C@@H:19]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[OH:20].[NH2:1][C@H:2]([CH2:8][C:9]1[CH:14]=[C:13]([F:15])[C:12]([F:16])=[CH:11][C:10]=1[F:17])[CH2:3][C:4]([O:6][CH3:7])=[O:5]

参加物

5

反応物 3

HCID 962WaterHCID 11914(-)-Mandelic acidHCID 49820754Methyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate

生成物 1

HCID 49784071(R)-Methyl 3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-2-hydroxy-2-phenylacetate収率 80%

試薬・触媒・溶媒 1

HCID 3776Isopropanol溶媒

反応条件

温度
77.5 °C

実験手順

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.

後処理

  1. customto give a clear solution
  2. stirringAfter 15 minutes stirring
  3. additionAfter completion of the addition
  4. stirringthe reaction mixture was stirred at 25-30° C. for 3 hours
  5. customto give enantiomerically enriched crude methyl(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-(−)-mandelate as a white coloured product
  6. filtrationThe product was filtered
  7. washwashed with isopropanol (1.0 vol, 260 ml)
  8. customdried in a vacuum oven at 40-45° C. for 4-5 hours
  9. customto give enantiomerically enriched crude methyl(3R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate (R)-(−)-mandelate (135 gm, molar yield: 64%)
  10. customThe dried enantiomerically
  11. additionwas charged in isopropanol (20.0 vol, 2.7 Ltr) at 25-30° C.
  12. customto give a partially clear solution
  13. stirringThe clear solution was further stirred for 0.5 hour
  14. stirringAfter stirring for 0.5 hour
  15. temperaturethe clear solution was gradually cooled to 0-5° C. within 3 hours

出典と根拠

ORDレコード
ord-59b404d18fb640eeb7cad9576fe3f832
出典データセット
uspto-grants-2014_09
特許番号
US08846916B2

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