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

HRID 530565Notes

Reaction equation

HRID 530565 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 6994743Npc168081HCID 866999375-Phenyl-pentyl-2-oxopyridine-1-carboxylate

Product 1

HCID 86700008(2S*,3R*)-3-hydroxy-4-methyl-2-(5-phenylpentoxy-carbonylamino)-pentanoic acidYield 41.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (2S*,3R*)-2-amino-3-hydroxy-4-methyl-pentanoic acid (0.152 g, 1.04 mmol) and NaHCO3 (0.088 g, 1.05 mmol) in H2O (6.0 mL), at rt, the isomeric mixture containing 5-phenyl-pentyl-2-pyridyl-carbonate and 5-phenyl-pentyl-2-oxopyridine-1-carboxylate (0.96 g, 1.21 mmol) [prepared as for example 32, step 1] in THF (6.0 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 (0.145 g, 41%), as a yellowish 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 0.80 (d, J=6.63 Hz, 3H), 0.93 (d, J=6.49 Hz, 3H), 1.28-1.41 (m, 2H), 1.50-1.69 (m, 4H), 1.81-1.91 (m, 1H), 2.57 (d, J=7.67 Hz, 2H), 3.47 (d, J=8.36 Hz, 1H), 3.89-3.99 (m, 2H), 4.15 (dd, J=2.83, 9.47 Hz, 1H), 4.58 (s, 1H), 6.64 (d, J=9.43 Hz, 1H), 7.10-7.32 (m, 5H), 12.43 (s, 1H).

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-98fd4ebc254e4f0aa8d2a1df322c5f99
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

Loading…