HCID 54363709, compound → HCID 54401458, compound

HRID 1376624Notes

Reaction equation

HRID 1376624 reaction equation
[C:1]([O:4][CH2:5][C@H:6]([C:14]([NH:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][N:22]=1)=O)[NH:7][C:8](=[O:13])[C:9]([F:12])([F:11])[F:10])(=[O:3])[CH3:2]>P(Cl)(Cl)(Cl)=O>[C:1]([O:4][CH2:5][C@@H:6]([C:14]1[N:22]2[C:18]([S:19][CH:20]=[CH:21]2)=[CH:17][N:16]=1)[NH:7][C:8](=[O:13])[C:9]([F:12])([F:11])[F:10])(=[O:3])[CH3:2]

Participants

3

Reactant 1

HCID 54363709HCID 54363709, compound

Product 1

HCID 54401458HCID 54401458, compoundYield 67%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Procedure

To 0.506 g of the above-obtained 2-[(O-acetyl-N-trifluoroacetyl-D-seryl)amino]methylthiazole was added 10 ml of phosphorus oxychloride. The mixture was refluxed for 5 hours, cooled to room temperature, and then concentrated to dryness under reduced pressure. To the residue was added 50 ml of methylene chloride, and the mixture was thoroughly stirred. To this was added 30 ml of a saturated aqueous solution of sodium hydrogencarbonate with ice-cooling, and the mixture was stirred for an additional 30 minutes. Insoluble matters were removed by filtration. The organic layer was separated, and the aqueous layer was extracted with 30 ml of methylene chloride. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by flash column chromatography using silica gel, eluting with a 2:1 mixture of ethyl acetate and hexane to give 0.319 g (yield 67%) of 5-[(R)-2-acetoxy-1-(trifluoroacetyl-amino)ethyl]imidazo[5,1-b]thiazole. NMR (CDCl3) d: 2.08 (3H, s), 4.53 (1H, dd, J=11.6 Hz, 5.3 Hz), 4.57 (1H, dd, J=11.6 Hz, 7.8 Hz), 5.67 (1H, td, J=7.8 Hz, 5.3 Hz), 6.92 (1H, d, J=4.3 Hz), 7.05 (1H, s), 7.56 (1H, d, J=4.3 Hz), 7.64-7.74 (1H, br)

Workup

  1. temperatureThe mixture was refluxed for 5 hours
  2. concentrationconcentrated to dryness under reduced pressure
  3. additionTo the residue was added 50 ml of methylene chloride
  4. additionTo this was added 30 ml of a saturated aqueous solution of sodium hydrogencarbonate with ice-
  5. temperaturecooling
  6. stirringthe mixture was stirred for an additional 30 minutes
  7. customInsoluble matters were removed by filtration
  8. customThe organic layer was separated
  9. extractionthe aqueous layer was extracted with 30 ml of methylene chloride
  10. dry with materialThe combined organic layers were dried over anhydrous magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customThe residue was purified by flash column chromatography
  13. washeluting with a 2:1 mixture of ethyl acetate and hexane

Sources & evidence

ORD record
ord-2854b68a756b4bb888723e13648b0edc
Source dataset
uspto-grants-1997_09
Patent number
US05663162

Reaction notes

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