Acetic Anhydride → HCID 53940190, compound

HRID 1376629Notes

Reaction equation

HRID 1376629 reaction equation
C([O:4][CH2:5][C@H:6]([C:14]1[N:21]2[C:17]([S:18][CH:19]=[CH:20]2)=[CH:16][N:15]=1)[NH:7][C:8](=[O:13])C(F)(F)F)(=O)C.[OH-].[Na+].N[C@H](C1N2C(SC=C2)=CN=1)CO.C(OC(=O)C)(=O)C.C(=O)([O-])[O-].[K+].[K+]>CO.O.C(O)=O.C(Cl)Cl>[CH:8]([NH:7][C@@H:6]([C:14]1[N:21]2[C:17]([S:18][CH:19]=[CH:20]2)=[CH:16][N:15]=1)[CH2:5][OH:4])=[O:13]

Participants

10

Reactant 5

HCID 7918Acetic AnhydrideHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 54307345HCID 54307345, compoundHCID 54401457HCID 54401457, compound

Product 1

HCID 53940190HCID 53940190, compoundYield 89.6%

Reagents, catalysts & solvents 4

HCID 284Formic AcidSolventHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To the solution of 0.747 g of 5-[(S)-2-acetoxy-1-(trifluoroacetylamino)-ethyl]imidazo[5,1-b]thiazole in 10 ml of methanol was added 5 ml of an aqueous solution of 0.233 g of sodium hydroxide, and the mixture was then stirred at room temperature for 14 hours. The reaction mixture was concentrated to dryness under reduced pressure to give solid product containing 5-[(R)-1-amino-2-hydroxyethyl]imidazo[5,1-b]thiazole. To this product was added 50 ml of methylene chloride, and the mixture was stirred well. The mixture of 1.2 g of acetic anhydride and 2.7 g of formic acid which had been preliminarily heated to 50° C. for 10 minutes and cooled to room temperature was added to the suspension. After mixing at room temperature for 30 minutes, the mixture was cooled to room temperature. Water (5 ml) and potassium carbonate (5 g) were added, and the resulting mixture was stirred at room temperature for 30 minutes. Methanol (20 ml) was added, and the mixture was further stirred for i hour. The organic layer was separated by decantation. The aqueous layer containing crystalline products was washed five times with 20 ml of methylene chloride, and the methylene chloride layers were combined with the organic layer separated previously. The combined organic layer was dried with anhydrous potassium carbonate and concentrated to dryness, and the residue was purified on Sephadex LH20 (eluent: chloroform-methanol=1:1) to give 0.440 g of 5-((S)-1-formylamino-2-hydroxyethyl)imidazo[5,1-b]thiazole. Quantitative yield. NMR (CDCl3) δ: 3.90 (1H, dd, J=11.6 Hz, 3.6 Hz), 4.42 (1H, dd, J=11.6 Hz, 2.0 Hz), 5.45 (1H, ddd, J=9.0 Hz, 3.6 Hz, 2.0 Hz), 6.8-6.9 (1H, br), 6.83 (1H, d, J=4.3 Hz), 6.97 (1H, s), 7.76 (1H, d, J=4.3 Hz), 8.26 (1H, s). MS (EI, DMSO, 200° C.): 211 (M+).

Workup

  1. concentrationThe reaction mixture was concentrated to dryness under reduced pressure
  2. customto give solid product
  3. stirringthe mixture was stirred well
  4. temperaturehad been preliminarily heated to 50° C. for 10 minutes
  5. temperaturecooled to room temperature
  6. additionwas added to the suspension
  7. additionAfter mixing at room temperature for 30 minutes
  8. temperaturethe mixture was cooled to room temperature
  9. stirringthe resulting mixture was stirred at room temperature for 30 minutes
  10. stirringthe mixture was further stirred for i hour
  11. customThe organic layer was separated by decantation
  12. additionThe aqueous layer containing crystalline products
  13. washwas washed five times with 20 ml of methylene chloride
  14. customseparated previously
  15. dry with materialThe combined organic layer was dried with anhydrous potassium carbonate
  16. concentrationconcentrated to dryness
  17. customthe residue was purified on Sephadex

Sources & evidence

ORD record
ord-acc98a7b68cc48679749ff7349960388
Source dataset
uspto-grants-1997_09
Patent number
US05663162

Reaction notes

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