Hydrochloric Acid → (S)-4-[4-[2-[6-(Methylamino)pyridin-2-yl]ethoxy]phenyl]-3-(pyridin-3-yl)butanoic acid

HRID 1816018Notes

Reaction equation

HRID 1816018 reaction equation
[OH-].[Na+].[CH3:3][NH:4][C:5]1[N:10]=[C:9]([CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C@H:21]([C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[CH2:22][C:23]([O:25]CC)=[O:24])=[CH:16][CH:15]=2)[CH:8]=[CH:7][CH:6]=1.Cl>O1CCOCC1.O.C(Cl)Cl>[CH3:3][NH:4][C:5]1[N:10]=[C:9]([CH2:11][CH2:12][O:13][C:14]2[CH:19]=[CH:18][C:17]([CH2:20][C@H:21]([C:28]3[CH:29]=[N:30][CH:31]=[CH:32][CH:33]=3)[CH2:22][C:23]([OH:25])=[O:24])=[CH:16][CH:15]=2)[CH:8]=[CH:7][CH:6]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59997613Ethyl (S)-4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-(pyridin-3-yl)butanoate

Product 1

HCID 67173908(S)-4-[4-[2-[6-(Methylamino)pyridin-2-yl]ethoxy]phenyl]-3-(pyridin-3-yl)butanoic acidYield 92.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
50 °C

Procedure

2.0 M NaOH (15 mL, 30 mmole) was added to a solution of ethyl (S)-4-[4-[2-[6-(methylamino)pyridin-2-yl]ethoxy]phenyl]-3-(pyridin-3-yl)butanoate (9.2 g, 22 mmole) in dioxane/H2O (100 mL), and the mixture was heated at 50° C. After 18 hr, the reaction was cooled to RT, acidified with 10% HCl (25 mL), and concentrated to 1/3 volume to precipitate a gum. The supernatant was decanted and the gum was partitioned between H2O and CHCl3. The layers were separated and the aqueous layer was extracted with CHCl3 (3×). The combined organic layers were dried (MgSO4)and concentrated, and the residue was taken up in H2O and 2 M NaOH (30 mL). The solution was washed with Et2O (3×), and the Et2O extracts were discarded. The aqueous solution was acidified with 10% HCl (50 mL), concentrated to 1/3 volume, and extracted with CHCl3 (3×). The organic layers were combined, dried (MgSO4), and concentrated to leave a foam. This foam was taken up in CH2Cl2, and the solution was diluted with hexanes and concentrated. This process was repeated three times. The resulting solid was dried in vacuo at 65° C. to afford the title compound (7.96 g, 92%): 1H NMR (400 MHz, MeOH-d4) δ 88.28 (narrow m, 1 H), 8.21 (d, J=1.7 Hz, 1 H), 7.68 (narrow m, 1 H), 7.48 (dd, J=8.5, 7.3 Hz, 1 H), 7.30 (dd, J=7.9, 4.9 Hz, 1 H), 6.91 (d, J=8.6 Hz, 2 H), 6.72 (d, J=8.6 Hz, 2 H), 6.56 (d, J=7.3 Hz, 1 H), 6.44 (d, J=8.5 Hz, 1 H), 4.20 (t, J=6.6 Hz, 2 H), 3.31-3.42 (m, 1 H), 3.02 (t, J=6.6 Hz, 2 H), 2.97 (dd, J=13.6, 6.5 Hz, 1 H), 2.87 (s, 3 H), 2.77 (dd, J=13.6, 8.9 Hz, 1 H), 2.71 (dd, J=15.6, 6.4 Hz, 1 H), 2.62 (dd, J=15.6, 8.9 Hz, 1 H); MS (ES) m/e 392 (M+H)+. Anal. Calcd for C23H25N3O3.0.1H2O: C, 70.25; H, 6.46; N, 10.68. Found: C, 70.32; H, 6.50; N, 10.32.

Workup

  1. temperaturethe reaction was cooled to RT
  2. concentrationconcentrated to 1/3 volume
  3. customto precipitate a gum
  4. customThe supernatant was decanted
  5. customthe gum was partitioned between H2O and CHCl3
  6. customThe layers were separated
  7. extractionthe aqueous layer was extracted with CHCl3 (3×)
  8. concentrationconcentrated
  9. washThe solution was washed with Et2O (3×)
  10. concentrationconcentrated to 1/3 volume
  11. extractionextracted with CHCl3 (3×)
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated
  14. customto leave a foam
  15. concentrationconcentrated
  16. customThe resulting solid was dried in vacuo at 65° C.

Sources & evidence

ORD record
ord-985a79fcc6c64f09bdc880b22568d0b4
Source dataset
uspto-grants-2005_04
Patent number
US06881736B1

Reaction notes

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