Water → HCID 67518168, compound

HRID 2173430Notes

Reaction equation

HRID 2173430 reaction equation
O[CH:2]1[CH2:7][N:6]([C:8]([O:10][CH2:11][CH:12]2[C:24]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[C:18]3[C:13]2=[CH:14][CH:15]=[CH:16][CH:17]=3)=[O:9])[CH2:5][CH2:4][N:3]1[C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26].C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.C(Cl)Cl.O>C1COCC1>[N:3]1([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH:2]=[CH:7][N:6]([C:8]([O:10][CH2:11][CH:12]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=3[C:19]3[C:24]2=[CH:23][CH:22]=[CH:21][CH:20]=3)=[O:9])[CH2:5][CH2:4]1

Participants

6

Reactant 4

HCID 962WaterHCID 6344DichloromethaneHCID 9845Trifluoroacetic anhydrideHCID 67517692HCID 67517692, compound

Product 1

HCID 67518168HCID 67518168, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

In a round bottom flask charged with stirring bar, 1-tert-butyl 4-(9H-fluoren-9-ylmethyl) 2-hydroxypiperazine-1,4-dicarboxylate (4.34 g, 10.2 mmol) was dissolved in THF (100 mL) and was cooled down to 0° C. under N2. Then TFAA (1.589 mL, 11.25 mmol) was added. After stirring at 0° C. for 20 minutes, reaction was quenched by adding saturated aq. NaHCO3 and warmed up to room temperature. Then reaction was diluted by adding 200 mL of DCM and 100 mL of water. Layers were separated and aqueous layer was extracted with 100 mL of DCM. Organic phases were combined and dried over anhydrous Na2SO4. Removing solvent gave crude product that was purified by ISCO (120 gram silica gel column, 0-50% EtOAc/Hexane gradient). Concentration gave the title compound. 1H NMR (ppm) (500 MHz, CDCl3): δ 7.81 (2H, d, J=7.59 Hz), 7.61 (2H, dd, J=13.92, 7.51 Hz), 7.44 (2H, t, J=7.49 Hz), 7.35 (2H, t, J=7.47 Hz), 6.27-6.14 (2H, m), 4.52 (2H, dd, J=19.02, 6.70 Hz), 4.31 (1H, t, J=6.89 Hz), 3.81-3.68 (4H, m), 1.54 (9H, s); LC/MS (M+23)+=429.13;

Workup

  1. additionIn a round bottom flask charged
  2. stirringAfter stirring at 0° C. for 20 minutes
  3. customreaction
  4. customwas quenched
  5. additionby adding saturated aq. NaHCO3
  6. temperaturewarmed up to room temperature
  7. customThen reaction
  8. additionwas diluted
  9. customLayers were separated
  10. extractionaqueous layer was extracted with 100 mL of DCM
  11. dry with materialdried over anhydrous Na2SO4
  12. customRemoving solvent gave crude product that
  13. customwas purified by ISCO (120 gram silica gel column, 0-50% EtOAc/Hexane gradient)
  14. concentrationConcentration

Sources & evidence

ORD record
ord-d7d1da04d5b04a93b3d59b2c25745518
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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