Trifluoroacetic acid → HCID 2756129, compound

HRID 2277100Notes

Reaction equation

HRID 2277100 reaction equation
FC(F)(F)C(O)=O.[C:8]([O:12][C:13]([N:15]1[CH2:20][CH2:19][S:18][CH2:17][C@H:16]1[C:21]([OH:23])=[O:22])=[O:14])([CH3:11])(C)C.C([O-])(O)=O.[Na+].C(Cl)(OCC1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[C:39]2[C:34]1=[CH:35][CH:36]=[CH:37][CH:38]=2)=O>C(Cl)Cl.O1CCOCC1>[CH:44]1[C:45]2[CH:11]([CH2:8][O:12][C:13]([N:15]3[CH2:20][CH2:19][S:18][CH2:17][C@H:16]3[C:21]([OH:23])=[O:22])=[O:14])[C:34]3[C:39](=[CH:38][CH:37]=[CH:36][CH:35]=3)[C:40]=2[CH:41]=[CH:42][CH:43]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 343679-Fluorenylmethyl chloroformateHCID 516892Sodium BicarbonateHCID 2755966(R)-4-Boc-thiomorpholine-3-carboxylic acid

Product 1

HCID 2756129HCID 2756129, compoundYield 66.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

Trifluoroacetic acid (4 mL, 23.5 mmol) was added to a stirred solution of (R)-4-(tert-butoxy carbonyl)thiomorpholine-3-carboxylic acid (1.0 g, 4.05 mmol) in CH2Cl2 (20 mL), and the reaction mixture was stirred at room temperature for 2 h. Volatile byproducts were removed at reduced pressure and the residue was concentrated from toluene (2×20 mL) and dried under high vacuum for 30 min. The crude residue was dissolved in 1,4-dioxane (10 mL) and water (10 mL) was added followed by NaHCO3 (1.02 g, 12.15 mmol) and a solution of FMOC-Cl (1.04 g, 4.05 mmol) in 1,4-dioxane (10 mL). The reaction mixture was stirred at room temperature for 16 h. The mixture was concentrated under reduced pressure to remove volatile organic solvent and the residue was washed with MTBE (2×20 mL). The aqueous layer was acidified with 1N aqueous HCl to pH 2 and extracted with EtOAc (3×50 mL). The combined organic extracts were washed with brine solution (50 mL), dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by reverse phase column chromatography (C18; eluent: 10-100% acetonitrile/water) to afford the title compound (1.00 g) as a white semi-solid.

Workup

  1. customVolatile byproducts were removed at reduced pressure
  2. concentrationthe residue was concentrated from toluene (2×20 mL)
  3. customdried under high vacuum for 30 min
  4. dissolutionThe crude residue was dissolved in 1,4-dioxane (10 mL)
  5. additionwater (10 mL) was added
  6. stirringThe reaction mixture was stirred at room temperature for 16 h
  7. concentrationThe mixture was concentrated under reduced pressure
  8. customto remove volatile organic solvent
  9. washthe residue was washed with MTBE (2×20 mL)
  10. extractionextracted with EtOAc (3×50 mL)
  11. washThe combined organic extracts were washed with brine solution (50 mL)
  12. dry with materialdried over anhydrous Na2SO4
  13. filtrationfiltered
  14. concentrationconcentrated
  15. customThe residue was purified by reverse phase column chromatography (C18; eluent: 10-100% acetonitrile/water)

Sources & evidence

ORD record
ord-82e6413a6e654b369843faaf30ec94be
Source dataset
uspto-grants-2015_09
Patent number
US09133147B2

Reaction notes

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