Hydrochloric Acid → HCID 21715924, compound

HRID 1019273Notes

Reaction equation

HRID 1019273 reaction equation
C([S:4][CH:5]([CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:6]([NH:8][CH:9]1[C:15](=[O:16])[N:14]([CH2:17][C:18]([O:20]CC)=[O:19])[C:13]([CH3:24])([CH3:23])[CH2:12][CH2:11][CH2:10]1)=[O:7])(=O)C.[OH-].[Na+].Cl>CO.SCC(C(CS)O)O>[SH:4][CH:5]([CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)[C:6]([NH:8][CH:9]1[C:15](=[O:16])[N:14]([CH2:17][C:18]([OH:20])=[O:19])[C:13]([CH3:23])([CH3:24])[CH2:12][CH2:11][CH2:10]1)=[O:7]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium Hydroxide2×HCID 85391661HCID 85391661, compound

Product 1

HCID 21715924HCID 21715924, compoundYield 890%

Reagents, catalysts & solvents 2

HCID 190011,4-Dimercapto-2,3-butanediolCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

[S-(R*,R*)]-Hexahydro-6-[[2-(acetylthio)-1-oxo-3-phenylpropyl]amino]-2,2-dimethyl-7-oxo-1H-azepine-1-acetic acid, ethyl ester (2.0 g, 4.46 mmole) [prepared as described in Example 66 (g) of U.S. Pat. No. 5,552,397] was dissolved in methanol (9 ml) in a 100-ml flask equipped with an addition funnel, internal temperature probe and argon inlet. To the solution was added DL-dithiothreitol (34 mg, 0.22 mmole). The solution was sparged with argon for 15 minutes and then kept under argon. The resulting solution was cooled to 0° C. in an ice-bath. In the addition funnel, 1N sodium hydroxide (26.8 ml, 26.8 mmole) was sparged with argon for 30 minutes. The sparged sodium hydroxide solution was added to the reaction flask over 30 minutes so that the internal temperature did not exceed 5° C. The reaction was allowed to stir at 0° C. for 30 minutes and then the ice-bath was removed to allow the reaction to warm to room temperature over one hour. The reaction was stirred at room temperature for an additional 1.5 hours at which time TLC showed that the reaction was complete. A pH probe was attached to the reaction flask. The reaction was acidified with previously sparged 3N HCl to a pH of 6. A few seed crytals were added and the mixture was stirred for 5 minutes. The mixture was then further acidified to pH 2. The resulting slurry was stirred at room temperature for one hour. The product was collected by filtration and washed with distilled water until the wash-water tested negative for chloride with silver nitrate solution. The product was air-dried for 30 minutes, washed with t-butyl methyl ether (2×4 ml) and hexane (2×4 ml), air-dried, and dried under a high vacuum to give 1.5 g of title product as a white crystalline solid (890% yield),

Workup

  1. customequipped with an addition funnel
  2. customThe solution was sparged with argon for 15 minutes
  3. customdid not exceed 5° C
  4. customthe ice-bath was removed
  5. customthe reaction
  6. temperatureto warm to room temperature over one hour
  7. stirringThe reaction was stirred at room temperature for an additional 1.5 hours at which time TLC
  8. additionA few seed crytals were added
  9. stirringthe mixture was stirred for 5 minutes
  10. stirringThe resulting slurry was stirred at room temperature for one hour
  11. filtrationThe product was collected by filtration
  12. washwashed with distilled water until the
  13. washwash-water tested negative for chloride with silver nitrate solution
  14. customThe product was air-dried for 30 minutes
  15. washwashed with t-butyl methyl ether (2×4 ml) and hexane (2×4 ml)
  16. customair-dried
  17. customdried under a high vacuum

Sources & evidence

ORD record
ord-9d521415ba3f448d86184549225a9b4d
Source dataset
uspto-grants-2002_11
Patent number
US06486315B2

Reaction notes

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