Pyridine → (S)-2-(benzoyloxy)-4-(benzyloxycarbonylamino)butanoic acid

HRID 1949609Notes

Reaction equation

HRID 1949609 reaction equation
[CH2:1]([O:8][C:9]([NH:11][CH2:12][CH2:13][C@H:14]([OH:18])[C:15]([OH:17])=[O:16])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CC=CC=1.[C:25](Cl)(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1>C1COCC1.CN(C1C=CN=CC=1)C>[C:25]([O:18][C@@H:14]([CH2:13][CH2:12][NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])[C:15]([OH:17])=[O:16])(=[O:32])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 7412Benzoyl chlorideHCID 2733930(S)-2-Hydroxy-4-(((phenylmethoxy)carbonyl)amino)butyric acid

Product 1

HCID 58503128(S)-2-(benzoyloxy)-4-(benzyloxycarbonylamino)butanoic acidYield 51%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a stirring solution of (S)-4-(benzyloxycarbonylamino)-2-hydroxybutanoic acid (1, 612 g, 2.41 mol) in THF (6 L) at 0° C. was added DMAP (2.4 g) and pyridine (196 mL, 2.41 mol). After stirring for 20 minutes, benzoyl chloride (280 mL) was added slowly and the reaction was allowed to stir overnight at room temperature. The resulting precipitate was filtered and the filtrate was acidified with 1 M citric acid (1 L). The organic solvent was removed by rotary evaporation and the desired product was extracted with EtOAc (2×2 L). The combined organic layers were washed with 1 M citric acid (1 L), brine (1 L) and then dried over MgSO4. Solvent removal under vacuum resulted in a viscous oil, which was purified on a 6-inch reverse-phase HPLC column to yield (S)-2-(benzoyloxy)-4-(benzyloxycarbonylamino)butanoic acid (2) as a non-flowing viscous oil (439 g, 51% yield).

Workup

  1. stirringto stir overnight at room temperature
  2. filtrationThe resulting precipitate was filtered
  3. customThe organic solvent was removed by rotary evaporation
  4. extractionthe desired product was extracted with EtOAc (2×2 L)
  5. washThe combined organic layers were washed with 1 M citric acid (1 L), brine (1 L)
  6. dry with materialdried over MgSO4
  7. customSolvent removal under vacuum
  8. customresulted in a viscous oil, which
  9. customwas purified on a 6-inch reverse-phase HPLC column

Sources & evidence

ORD record
ord-d93126a2f8ba42a28863f775dba045ff
Source dataset
uspto-grants-2013_03
Patent number
US08399419B2

Reaction notes

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