Hydrochloric Acid → HCID 23000617, compound

HRID 397535Notes

Reaction equation

HRID 397535 reaction equation
[CH2:1]([O:3][C:4](=[O:31])[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:22])([F:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[C:7]=1[F:30])[CH3:2].Cl>CCOC(C)=O>[CH2:1]([O:3][C:4](=[O:31])[CH2:5][C:6]1[CH:11]=[CH:10][N:9]=[C:8]([NH:12][CH2:13][C:14]([F:22])([F:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[C:7]=1[F:30])[CH3:2]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 23000614HCID 23000614, compound

Product 1

HCID 23000617HCID 23000617, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

Through a 0° C. solution of 0.218 g (0.496 mmol) ethyl {2-[(tert-butoxycarbonyl)(2,2-difluoro-2-pyridin-2-ylethyl)amino]-3-fluoropyridin-4-yl}acetate 29-1 in 10 mL EtOAc was passed a steady stream of HCl gas for 10 min. The reaction was stirred at 0° C. for 1.5 h and then at room temperature for 10 min. The reaction mixture was then flushed with N2 and poured onto 150 mL EtOAc/50 mL 2M NaOH/7 mL conc NaOH. The layers were mixed and then separated. The aqueous layer was back extracted with 50 mL EtOAc. The combined organics were washed w/50 mL water and 50 mL brine, dried over Na2SO4, filtered, and concentrated in vacuo. Purification by automated flash chromatography (40 g silica cartridge, linear gradient 0-50% EtOAc/hexane over 30 min, 30 mL/min flow rate) gave ethyl {2-[(2,2-difluoro-2-pyridin-2-ylethyl)amino]-3-fluoropyridin-4-yl}acetate 29-2. 1H NMR (CDCl3, 400 MHz) δ8.663 (d, 1H, J=4.67 Hz, ArH); 7.829-7.790 (m, 2H, ArH); 7.693 (d, 1H, J=7.14 Hz, ArH); 7.377 (t, 1H, J=6.14 Hz, ArH); 6.489 (t, 1H, J=4.99 Hz, ArH); 4.492-4.405 (m, 2H, CH2); 4.199-4.145 (m, 2H, CH2); 3.585 (s, 2H, CH2); 1.276-1.237 (m, 3H, CH3); MS (Electrospray): m/z 340.1 (M+H).

Workup

  1. customThrough a 0° C.
  2. customfor 10 min
  3. waitat room temperature for 10 min
  4. customThe reaction mixture was then flushed with N2
  5. additionpoured onto 150 mL EtOAc/50 mL 2M NaOH/7 mL conc NaOH
  6. additionThe layers were mixed
  7. customseparated
  8. extractionThe aqueous layer was back extracted with 50 mL EtOAc
  9. washThe combined organics were washed w/50 mL water and 50 mL brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customPurification by automated flash chromatography (40 g silica cartridge, linear gradient 0-50% EtOAc/hexane over 30 min, 30 mL/min flow rate)

Sources & evidence

ORD record
ord-e8241f51367847958ea6c68c890fe954
Source dataset
uspto-grants-2003_08
Patent number
US06610701B2

Reaction notes

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