Hydrochloric Acid → HCID 59085882, compound

HRID 397537Notes

Reaction equation

HRID 397537 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([N:12](C(OC(C)(C)C)=O)[CH2:13][C:14]([F:23])([F:22])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N+:16]=2[O-:21])[C:7]=1[F:31])[CH3:2].Cl>CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:32])[CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][CH2:13][C:14]([F:23])([F:22])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N+:16]=2[O-:21])[C:7]=1[F:31])[CH3:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 59085851HCID 59085851, compound2×

Product 1

HCID 59085882HCID 59085882, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Through a 0° C. solution of 0.221 g (0.485 mmol) ethyl(2-{(tert-butoxycarbonyl)[2,2-difluoro-2-(1-oxidopyridin-2-yl)ethyl]amino}-3-fluoropyridin-4-yl)acetate 30-1, contaminated with ethyl(2-{(tert-butoxycarbonyl)[2,2-difluoro-2-(1-oxidopyridin-2-yl)ethyl]amino}-3-fluoropyridin-4-yl)acetate, in 3 mL EtOAc was passed a steady stream of HCl gas for 20 min. The reaction was stirred at 0° C. for 20 min. The mixture was then flushed with N2 and poured onto 200 mL EtOAc/50 mL 2.0M NaOH/7 mL conc NaOH. The layers were mixed and then separated. The aqueous layer was back extracted with 25 mL EtOAc. The combined organics were washed w/100 mL water and 100 mL brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by automated flash chromatography (40 g silica cartridge, linear gradient 0-5% MeOH/CH2Cl2 over 30 min, 30 mL/min flow rate) provided ethyl(2-{[2,2-difluoro-2-(1-oxidopyridin-2-yl)ethyl]amino}-3-fluoropyridin-4-yl)acetate 30-2. 1H NMR (CDCl3, 400 MHz) δ8.288 (d, 1H, J=6.41 Hz, ArH); 7.727 (d, 1H, J=5.13 Hz, ArH); 7.622 (dd, 1H, J=2.20 Hz, 7.87 Hz, ArH); 7.363-7.323 (m, 1H, ArH); 7.297-7.257 (m, 1H, ArH); 6.455 (t, 1H, J=4.95 Hz, ArH); 4.751-4.663 (m, 2H, CH2); 4.164 (dd, 2H, J=7.14 Hz, 14.28 Hz, CH2); 3.560 (s, 2H, CH2); 1.254 (t, 3H, J=7.15 Hz, CH3); MS (Electrospray): m/z 356.1 (M+H).

Workup

  1. customThrough a 0° C.
  2. customfor 20 min
  3. customThe mixture was then flushed with N2
  4. additionpoured onto 200 mL EtOAc/50 mL 2.0M NaOH/7 mL conc NaOH
  5. additionThe layers were mixed
  6. customseparated
  7. extractionThe aqueous layer was back extracted with 25 mL EtOAc
  8. washThe combined organics were washed w/100 mL water and 100 mL brine
  9. dry with materialdried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customPurification by automated flash chromatography (40 g silica cartridge, linear gradient 0-5% MeOH/CH2Cl2 over 30 min, 30 mL/min flow rate)

Sources & evidence

ORD record
ord-785fa6f7e64d496584b5a3758f820c03
Source dataset
uspto-grants-2003_08
Patent number
US06610701B2

Reaction notes

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