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

HRID 530553Notes

Reaction equation

HRID 530553 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 10953556(2S,3R)-3-HydroxynorvalineHCID 866999375-Phenyl-pentyl-2-oxopyridine-1-carboxylate

Product 1

HCID 86699994(2S*,3R*)-3-hydroxy-2-(5-phenylpentoxy-carbonylamino)-pentanoic acidYield 46.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (2S*,3R*)-2-amino-3-hydroxy-pentanoic acid (0.068 g, 0.51 mmol) and NaHCO3 (0.128 g, 1.53 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 (0.218 g, 0.77 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 (0.076 g, 46% over 3 steps), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 324 [M−NH4]+; (ESI) m/z: 322 [M−H]−. 1H NMR (DMSO-d6) δ 0.85 (t, J=7.38 Hz, 3H), 1.28-1.49 (m, 4H), 1.50-1.68 (m, 4H), 2.58 (t, J=7.67 Hz, 2H), 3.79 (td, J=2.93, 6.83 Hz, 1H), 3.97 (t, J=6.60 Hz, 2H), 3.99-4.11 (m, 1H), 6.63 (d, J=9.23 Hz, 1H), 7.12-7.32 (m, 5H).

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-9f53779c474a4b52a46926cb759bfa64
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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