Sodium Bicarbonate → (2R*,3S*)-3-hydroxy-4-methyl-2-(5-phenylpentoxy-carbonylamino)-pentanoic acid

HRID 530558Notes

Reaction equation

HRID 530558 reaction equation
[NH2:1][C@H:2]([C@@H:6]([OH:10])[CH:7]([CH3:9])[CH3:8])[C:3]([OH:5])=[O:4].[C:11]([O-:14])(O)=[O:12].[Na+].[C:16]1([CH2:22][CH2:23][CH2:24][CH2:25][CH2:26]C2C(=O)N(C([O-])=O)C=CC=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>O.C1COCC1>[OH:10][C@@H:6]([CH:7]([CH3:9])[CH3:8])[C@@H:2]([NH:1][C:11]([O:14][CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)=[O:12])[C:3]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2724869(2R,3S)-2-amino-3-hydroxy-4-methylpentanoic acidHCID 866999375-Phenyl-pentyl-2-oxopyridine-1-carboxylate

Product 1

HCID 86700000(2R*,3S*)-3-hydroxy-4-methyl-2-(5-phenylpentoxy-carbonylamino)-pentanoic acidYield 59%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred diastereomeric mixture containing (2R*,3R*)- and (2R*,3S*)-2-amino-3-hydroxy-4-methyl-pentanoic acid (0.058 g, 0.4 mmol) and NaHCO3 (0.035 g, 0.4 mmol) in H2O (2.0 mL), at rt, the isomeric mixture containing 5-phenyl-pentyl-2-pyridyl-carbonate and 5-phenyl-pentyl-2-oxopyridine-1-carboxylate (0.38 g, 1.4 mmol) [prepared as for example 32, 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 (0.079 g, 59% 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: 338 [M−H]+; (ESI) m/z: 336 [M−H]−. 1H NMR (DMSO-d6) δ 0.81 (d, J=6.69 Hz, 3H), 0.88 (d, J=6.77 Hz, 3H), 1.32 (tt, J=5.81, 9.52 Hz, 2H), 1.57 (td, J=4.08, 8.39 Hz, 4H), 1.70-1.84 (m, 1H), 2.56 (t, J=7.71 Hz, 2H), 3.40 (t, J=6.09 Hz, 1H), 3.93 (t, J=6.61 Hz, 2H), 3.96-4.04 (m, 1H), 4.84 (s, 1H), 7.12-7.21 (m, 4H), 7.27 (t, J=7.49 Hz, 2H), 12.00-12.96 (s, 1H) (reported data refer to the major anti diastereoisomer).

Workup

  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

Sources & evidence

ORD record
ord-abb23bf0ecb74c11936f264a767e441f
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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