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

HRID 530546Notes

Reaction equation

HRID 530546 reaction equation
[NH2:1][C@H:2]([C@@H:6]([OH:9])[CH2:7][CH3:8])[C:3]([OH:5])=[O:4].[C:10]([O-:13])(O)=[O:11].[Na+].[C:15]1([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]C2C(=O)N(C([O-])=O)C=CC=2)[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>O.C1COCC1>[OH:9][C@@H:6]([CH2:7][CH3:8])[C@@H:2]([NH:1][C:10]([O:13][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)=[O:11])[C:3]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 642223(3S)-3-Hydroxy-D-norvalineHCID 866999375-Phenyl-pentyl-2-oxopyridine-1-carboxylate

Product 1

HCID 86699983(2R*,3S*)-3-hydroxy-2-(5-phenylpentoxy-carbonylamino)-pentanoic acidYield 60%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred diastereomeric mixture containing (2R*,3R*) and (2R*,3S*)-2-amino-3-hydroxy-pentanoic acid (0.107 g, 0.81 mmol) and NaHCO3 (0.102 g, 1.21 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 (0.346 g, 1.21 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 (0.155 g, 60% 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: 324[M−H]+; (ESI) m/z: 322 [M−H]−. 1H NMR (DMSO-d6) δ 0.86 (t, J=7.41 Hz, 3H), 1.27-1.50 (m, 4H), 1.51-1.67 (m, 4H), 2.57 (t, J=7.69 Hz, 2H), 3.52-3.66 (m, 1H), 3.93 (t, J=6.63 Hz, 3H), 4.83 (s, 1H), 7.10 (d, J=8.73 Hz, 1H), 7.13-7.22 (m, 3H), 7.22-7.30 (m, 2H), 12.35 (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-45021cdeaa0d490bbd07c630885970ae
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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