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

HRID 530577Notes

Reaction equation

HRID 530577 reaction equation
[NH2:1][C@@H:2]([C@H:6]([OH:11])[C:7]([CH3:10])([CH3:9])[CH3:8])[C:3]([OH:5])=[O:4].[C:12]([O-:15])(O)=[O:13].[Na+].[C:17]1([CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]C2C(=O)N(C([O-])=O)C=CC=2)[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>O.C1COCC1>[OH:11][C@@H:6]([C:7]([CH3:8])([CH3:10])[CH3:9])[C@@H:2]([NH:1][C:12]([O:15][CH2:27][CH2:26][CH2:25][CH2:24][CH2:23][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)=[O:13])[C:3]([OH:5])=[O:4]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 2725116(2S,3R)-2-Amino-3-Hydroxy-4,4-Dimethylpentanoic AcidHCID 866999375-Phenyl-pentyl-2-oxopyridine-1-carboxylate

Product 1

HCID 86700020(2R*,3S*)-3-hydroxy-4,4-dimethyl-2-(5-phenylpentoxy-carbonylamino)-pentanoic acidYield 44%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred mixture of (2S*,3R*)-2-amino-3-hydroxy-4,4-dimethyl-pentanoic acid (0.36 g, 2.24 mmol) and NaHCO3 (0.188 g, 2.24 mmol) in H2O (15 mL), at rt, the isomeric mixture containing 5-phenyl-pentyl-2-pyridyl-carbonate and 5-phenyl-pentyl-2-oxopyridine-1-carboxylate (1.95 g, 6.84 mmol) [prepared as for example 32, step 1] in THF (15 mL) was added. After 15 h at rt, the crude mixture was rotary evaporated to remove the organics and subsequently extracted with Et2O (3×40 mL). The aqueous phase was acidified with 2.0 M HCl solution to pH 2-3 and subsequently extracted with AcOEt (3×40 mL). The organic fraction was dried over Na2SO4, filtered and concentrated to dryness to afford the title compound (0.346 g, 44%), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 352 [M−H]+; (ESI) m/z: 350 [M−H]−. 1H NMR (DMSO-d6) δ 0.86 (s, 9H), 1.33 (tt, J=5.95, 9.00 Hz, 2H), 1.57 (ddt, J=3.93, 6.59, 10.94 Hz, 4H), 2.57 (t, J=7.70 Hz, 2H), 3.59 (s, 1H), 3.87-4.03 (m, 2H), 4.12-4.21 (m, 1H), 6.25 (d, J=9.37 Hz, 1H), 7.10-7.32 (m, 5H), 11.55 (s, 1H).

Workup

  1. additionwas added
  2. customthe crude mixture was rotary evaporated
  3. customto remove the organics and
  4. extractionsubsequently extracted with Et2O (3×40 mL)
  5. extractionsubsequently extracted with AcOEt (3×40 mL)
  6. dry with materialThe organic fraction was dried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-52c99e67155d4d8e9a3bcf22938bd641
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

Loading…