Hydrochloric Acid → (4S,5S)-5-((2S)-2-t-butyloxycarbonylamino-3-phenylpropyl)-4-benzyl-1,3-oxazolidin-2-one

HRID 2113913Notes

Reaction equation

HRID 2113913 reaction equation
C(O)(=O)CC[C:4](O)=[O:5].[NH2:9][C@H:10]([C@@H:18]([OH:36])[CH2:19][C@@H:20]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)[CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.C1C([N+]([O-])=O)=CC=C(OC(OCC2SC=NC=2)=O)C=1.Cl.C(=O)(O)[O-].[Na+].[OH-].[Na+].Cl>CCCCCCC.C1COCC1.O.C(OCC)(=O)C>[C:32]([O:31][C:29]([NH:28][C@@H:20]([CH2:21][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1)[CH2:19][C@@H:18]1[O:36][C:4](=[O:5])[NH:9][C@H:10]1[CH2:11][C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1)=[O:30])([CH3:33])([CH3:35])[CH3:34]

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 11997925(2S,3S,5S)-5-tert-Butyloxycarbonylamino-2-amino-3-hydroxy-1,6-diphenylhexane succinateHCID 218783405-Hydroxymethylthiazole 4-nitrophenylcarbonate hydrochloride

Product 1

HCID 66874692(4S,5S)-5-((2S)-2-t-butyloxycarbonylamino-3-phenylpropyl)-4-benzyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 4

HCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 8900HeptaneSolvent

Procedure

(2S,3S,5S)-2-Amino-3-hydroxy-5-t-butyloxycarbonylamino-1,6-diphenylhexane succinate salt (30 g, 63 mmol; U.S. Pat. No. 5,654,466), ((5-thiazolyl)methyl)-(4-nitrophenyl)carbonate hydrochloride (22.2 g; U.S. Pat. No. 5,597,926) and sodium bicarbonate (16.2 g) were mixed with 300 mL of water and 300 mL of ethyl acetate and the mixture was stirred at room temperature for about 30 minutes. The organic layer was then separated and heated at about 60° C. for 12 hours, and then stirred at 20-25° C. for 6 hours. 3 mL of ammonium hydroxide (29% ammonia in water) was added and the mixture stirred for 1.5 hours. The resulting mixture was washed with 4×200 mL of 10% aqueous potassium carbonate and the organic layer was separated and evaporated under vacuum to provide an oil. The oil was suspended in about 250 mL of heptane. The heptane was evaporated under vacuum to provide a yellow solid. The yellow solid was dissolved in 300 mL of THF and 25 mL of 10% aqueous sodium hydroxide was added. After stirring for about 3 hours, the mixture was adjusted to pH 7 by addition of 4N HCl (about 16 mL). The THF was evaporated under vacuum to leave an aqueous residue, to which was added 300 mL of distilled water. After stirring this mixture, a fine suspension of solids resulted. The solid was collected by filtration and the filtered solid was washed with water (1400 mL) in several portions, resulting in the desired product.

Workup

  1. customThe organic layer was then separated
  2. temperatureheated at about 60° C. for 12 hours
  3. stirringstirred at 20-25° C. for 6 hours
  4. addition3 mL of ammonium hydroxide (29% ammonia in water) was added
  5. stirringthe mixture stirred for 1.5 hours
  6. washThe resulting mixture was washed with 4×200 mL of 10% aqueous potassium carbonate
  7. customthe organic layer was separated
  8. customevaporated under vacuum
  9. customto provide an oil
  10. customThe heptane was evaporated under vacuum
  11. customto provide a yellow solid
  12. stirringAfter stirring for about 3 hours
  13. customThe THF was evaporated under vacuum
  14. customto leave an aqueous residue
  15. stirringAfter stirring this mixture
  16. additiona fine suspension of solids
  17. customresulted
  18. filtrationThe solid was collected by filtration
  19. washthe filtered solid was washed with water (1400 mL) in several portions

Sources & evidence

ORD record
ord-1e51a9d4c9bd4b6bb54445802308b573
Source dataset
uspto-grants-2008_10
Patent number
US07432294B2

Reaction notes

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