Trifluoroacetic acid → HCID 72949254, compound

HRID 1754837Notes

Reaction equation

HRID 1754837 reaction equation
FC(F)(F)C(O)=O.C([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]2[N:21]=[CH:22][S:23][C:17]=2[CH:16]1[C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[O:31][CH2:32][C:33]([O:35]CC)=[O:34])=[O:14])(C)(C)C.C(N(CC)CC)C.ClC(O[CH2:49][C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1)=O>C(Cl)Cl>[CH2:49]([O:12][C:13]([N:15]1[CH2:20][CH2:19][C:18]2[N:21]=[CH:22][S:23][C:17]=2[CH:16]1[C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[O:31][CH2:32][C:33]([OH:35])=[O:34])=[O:14])[C:50]1[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=1

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471Triethylamine2×HCID 10387Benzyl chloroformate2×HCID 90022830HCID 90022830, compound

Product 1

HCID 72949254HCID 72949254, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Trifluoroacetic acid (8.2 mL) was added to a solution of (±)-4-(2-ethoxycarbonylmethoxy-5-fluoro-phenyl)-6,7-dihydro-4H-thiazolo[5,4-c]pyridine-5-carboxylic acid tert-butyl ester (237 mg, 0.52 mmol, 1.0 eq.) in DCM (12 mL). The resulting mixture was stirred at r.t. for 5 hours. The solvent was removed in vacuo. To an-ice cooled suspension of the residue and triethylamine (0.11 mL, 0.79 mmol, 1.5 eq.) in DCM (5 mL), benzyl chloroformate (79 μL, 0.52 mmol, 1.0 eq.) was added dropwise. Upon completion of the addition, the cooling bath was removed and the suspension was stirred at r.t. for 18 hours. Triethylamine (0.11 mL, 0.79 mmol, 1.5 eq.) and benzyl chloroformate (39 μL, 0.26 mmol, 0.5 eq.) were added again. The mixture was stirred at r.t. for 18 hours. The reaction was quenched with 1M aq. citric acid soln. (12 mL). The layers were separated. The aq. phase was extracted with DCM (3×6 mL). The comb. org. phases were dried over MgSO4 and concentrated in vacuo. To a solution of the crude ester in THF (2.3 mL), 1M aq. NaOH soln. (0.7 mL) was added. The solution was stirred at r.t. for 18 hours. The solution was diluted with water (2 mL), 1M aq. HCl soln. (0.7 mL), and DCM. The layers were separated and the aq. phase was extracted with DCM (2×). The comb. org. phases were concentrated in vacuo. The residue was dissolved in DMF (1.2 mL), purified by prep. HPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions), and concentrated in vacuo to give the title compound as a pale yellow foam.

Workup

  1. customThe solvent was removed in vacuo
  2. temperatureTo an-ice cooled
  3. additionwas added dropwise
  4. additionUpon completion of the addition
  5. customthe cooling bath was removed
  6. stirringthe suspension was stirred at r.t. for 18 hours
  7. stirringThe mixture was stirred at r.t. for 18 hours
  8. customThe reaction was quenched with 1M aq. citric acid soln
  9. customThe layers were separated
  10. extractionThe aq. phase was extracted with DCM (3×6 mL)
  11. dry with materialphases were dried over MgSO4
  12. concentrationconcentrated in vacuo
  13. addition(0.7 mL) was added
  14. stirringThe solution was stirred at r.t. for 18 hours
  15. additionThe solution was diluted with water (2 mL), 1M aq. HCl soln
  16. customThe layers were separated
  17. extractionthe aq. phase was extracted with DCM (2×)
  18. concentrationphases were concentrated in vacuo
  19. dissolutionThe residue was dissolved in DMF (1.2 mL)
  20. custompurified by prep
  21. concentrationHPLC (column: Waters XBridge, 30×75 mm, 10 um, UV/MS, acidic conditions), and concentrated in vacuo

Sources & evidence

ORD record
ord-51cd66f5da84471a9ccfeef1eb46dd4c
Source dataset
uspto-grants-2015_10
Patent number
US09169270B2

Reaction notes

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