Sodium Bicarbonate → (2S*,3R*)-3-hydroxy-2-[(4-phenylphenyl)-methoxy-carbonylamino]-pentanoic acid

HRID 530555Notes

Reaction equation

HRID 530555 reaction equation
[NH2:1][C@@H:2]([C@H:6]([OH:9])[CH2:7][CH3:8])[C:3]([OH:5])=[O:4].C([O-])(O)=O.[Na+].[C:15](=O)([O-:36])[O:16][C:17]1C(C)=C(C2C=CC(C3C=CC=CC=3)=CC=2)C=CN=1.[C:38]1([C:44]2[CH:49]=[CH:48][C:47](C3C=CN(C([O-])=O)C(=O)C=3C)=[CH:46][CH:45]=2)[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1>O.C1COCC1>[OH:9][C@H:6]([CH2:7][CH3:8])[C@H:2]([N:1]([C:47]1[CH:46]=[CH:45][C:44]([C:38]2[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=2)=[CH:49][CH:48]=1)[C:15]([O:16][CH3:17])=[O:36])[C:3]([OH:5])=[O:4]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 10953556(2S,3R)-3-HydroxynorvalineHCID 86699987(4-Phenylphenyl)-methyl-2-pyridyl carbonateHCID 86699989(4-Phenylphenyl)-methyl-2-oxopyridine-1-carboxylate

Product 1

HCID 86699996(2S*,3R*)-3-hydroxy-2-[(4-phenylphenyl)-methoxy-carbonylamino]-pentanoic acidYield 93%

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 (4-phenylphenyl)-methyl-2-pyridyl carbonate and (4-phenylphenyl)-methyl-2-oxopyridine-1-carboxylate (0.233 g, 0.77 mmol) [prepared as for example 17, 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 (0.164 g, 93% over 3 steps), as an off-white solid, which was used in the next step without further purification. MS (ESI) m/z: 361 [M−NH4]+; (ESI) m/z: 342 [M−H]−. 1H NMR (DMSO-d6) δ 0.85 (t, J=7.38 Hz, 3H), 1.42 (p, J=7.31 Hz, 2H), 3.81 (td, J=3.02, 6.87 Hz, 1H), 4.07 (dd, J=3.04, 9.23 Hz, 1H), 4.66 (s, 1H), 5.10 (s, 2H), 6.92 (d, J=9.21 Hz, 1H), 7.28-7.56 (m, 5H), 7.59-7.78 (m, 4H), 12.59 (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-3800272eab0f4d24b80ff87de10d967e
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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