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

HRID 530567Notes

Reaction equation

HRID 530567 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([O-])(O)=O.[Na+].[C:16](=O)([O-:37])[O:17][C:18]1C(C)=C(C2C=CC(C3C=CC=CC=3)=CC=2)C=CN=1.[C:39]1([C:45]2[CH:50]=[CH:49][C:48](C3C=CN(C([O-])=O)C(=O)C=3C)=[CH:47][CH:46]=2)[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>O.C1COCC1>[OH:10][C@H:6]([CH:7]([CH3:9])[CH3:8])[C@H:2]([N:1]([C:48]1[CH:47]=[CH:46][C:45]([C:39]2[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=2)=[CH:50][CH:49]=1)[C:16]([O:17][CH3:18])=[O:37])[C:3]([OH:5])=[O:4]

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 6994743Npc168081HCID 86699987(4-Phenylphenyl)-methyl-2-pyridyl carbonateHCID 86699989(4-Phenylphenyl)-methyl-2-oxopyridine-1-carboxylate

Product 1

HCID 86700010(2S*,3R*)-3-hydroxy-4-methyl-2-[(4-phenylphenyl)-methoxy-carbonylamino]-pentanoic acidYield 52%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred diastereomeric mixture containing (2S*,3R*)-2-amino-3-hydroxy-4-methyl-pentanoic acid (0.156 g, 1.06 mmol) and NaHCO3 (0.09 g, 1.06 mmol) in H2O (5.0 mL), at rt, the isomeric mixture containing (4-phenylphenyl)-methyl-2-pyridyl carbonate and (4-phenylphenyl)-methyl-2-oxopyridine-1-carboxylate (1.4 g, 4.6 mmol) [prepared as for example 17, step 1] in THF (5.0 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 (0.196 g, 52% over two steps), as a yellowish solid, which was used in the next step without further purification. MS (ESI) m/z: 375 [M−NH4]+; (ESI) m/z: 356 [M−H]−. 1H NMR (DMSO-d6) δ 0.82 (d, J=6.66 Hz, 3H), 0.92 (d, J=6.39 Hz, 3H), 1.54-1.70 (m, 1H), 3.51 (t, J=8.38 Hz, 1H), 4.20 (dd, J=2.88, 9.42 Hz, 1H), 4.63 (d, J=8.86 Hz, 1H), 5.11 (s, 2H), 6.94 (d, J=9.44 Hz, 1H), 7.37 (t, J=6.55 Hz, 1H), 7.44-7.52 (m, 4H), 7.63-7.75 (m, 4H), 12.57 (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-ca170b897c3943afb05817f5079c4261
Source dataset
uspto-grants-2016_05
Patent number
US09353075B2

Reaction notes

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