Sodium Bicarbonate → (2R*,3S*)-3-hydroxy-2-[(4-phenylphenyl)-methoxycarbonylamino]-pentanoic acid

HRID 530548ノート

反応式

HRID 530548 の反応式
[NH2:1][C@H:2]([C@@H:6]([OH:9])[CH2:7][CH3:8])[C:3]([OH:5])=[O:4].C([O-])(O)=O.[Na+].[C:15](=O)([O-:36])[O:16][C:17]1C(C)=C(C2C=CC(C3C=CC=CC=3)=CC=2)C=CN=1.[C:38]1([C:44]2[CH:49]=[CH:48][C:47](C3C=CN(C([O-])=O)C(=O)C=3C)=[CH:46][CH:45]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O.C1COCC1>[OH:9][C@@H:6]([CH2:7][CH3:8])[C@@H:2]([N:1]([C:47]1[CH:46]=[CH:45][C:44]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)=[CH:49][CH:48]=1)[C:15]([O:16][CH3:17])=[O:36])[C:3]([OH:5])=[O:4]

参加物

7

反応物 4

HCID 516892Sodium BicarbonateHCID 642223(3S)-3-Hydroxy-D-norvalineHCID 86699987(4-Phenylphenyl)-methyl-2-pyridyl carbonateHCID 86699989(4-Phenylphenyl)-methyl-2-oxopyridine-1-carboxylate

生成物 1

HCID 86699986(2R*,3S*)-3-hydroxy-2-[(4-phenylphenyl)-methoxycarbonylamino]-pentanoic acid収率 74%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a stirred diastereomeric mixture containing (2R*,3R*) and (2R*,3S*)-2-amino-3-hydroxy-pentanoic acid (0.108 g, 0.81 mmol) and NaHCO3 (0.204 g, 2.43 mmol) in H2O (2.0 mL), at rt, the isomeric mixture containing (4-phenylphenyl)-methyl-2-pyridyl carbonate and (4-phenylphenyl)-methyl-2-oxopyridine-1-carboxylate (0.37 g, 1.22 mmol) [prepared as for example 17, step 1] in THF (2.0 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et2O (3×10 mL). The aqueous phase was acidified with 2.0 M HCl solution to pH 2-3 and subsequently extracted with AcOEt (3×20 mL). The organic fraction was dried over Na2SO4, filtered and concentrated to dryness to afford the title compound (0.206 g, 74% over 2 steps), as a diastereoisomeric mixture (anti:syn=8:2), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 361 [M−NH4]+; (ESI) m/z: 342 [M−H]−. 1H NMR (DMSO-d6) δ 0.87 (t, J=7.38 Hz, 3H), 1.36-1.55 (m, 2H), 3.55-3.69 (m, 1H), 3.94-4.05 (m, 1H), 4.73-4.99 (m, 1H), 5.08 (s, 2H), 7.29-7.54 (m, 6H), 7.57-7.77 (m, 4H), 11.38-13.49 (m, 1H) (reported data refer to the major anti diastereoisomer).

後処理

  1. additionwas added
  2. customthe crude mixture was rotary evaporated
  3. customto remove the organics and
  4. extractionsubsequently extracted with Et2O (3×10 mL)
  5. extractionsubsequently extracted with AcOEt (3×20 mL)
  6. dry with materialThe organic fraction was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

出典と根拠

ORDレコード
ord-9efb35cc09d04d57aa3061229be2a9ca
出典データセット
uspto-grants-2016_05
特許番号
US09353075B2

反応ノート

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