Lithium hydroxide, monohydrate → HCID 18462634, compound

HRID 2302010Notes

Reaction equation

HRID 2302010 reaction equation
C[O:2][C:3](=[O:26])[CH2:4][CH:5]1[CH2:14][CH2:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]3[N:25]=[CH:24][CH:23]=[CH:22][N:21]=3)[CH:11]=2)[CH2:6]1.O[Li].O>O1CCOCC1.O>[N:21]1[CH:22]=[CH:23][CH:24]=[N:25][C:20]=1[NH:19][CH2:18][CH2:17][CH2:16][O:15][C:10]1[CH:11]=[C:12]2[C:7](=[CH:8][CH:9]=1)[CH2:6][CH:5]([CH2:4][C:3]([OH:26])=[O:2])[CH2:14][CH2:13]2

Participants

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 69978017HCID 69978017, compound

Product 1

HCID 18462634HCID 18462634, compoundYield 16.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of {6-[3-(pyrimidin-2-ylamino)-propoxy]-1,2,3,4-tetrahydro-naphthalen-2-yl}-acetic acid methyl ester (0.09 g) in 1,4-dioxane (5 mL) was added a solution of LiOH.H2O (0.04 g) in H2O (2 mL) and the reaction was heated to 100° C. for 1 h. The reaction was cooled to room temperature and concentrated under reduced pressure. Water was added to the residue and the mixture was cooled in an ice bath. The mixture was brought to pH 5 by the addition of 1N HCl. The aqueous suspension was extracted with CH2Cl2 and CHCl3. The combined organic layers were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified using silica gel chromatography. Elution with 10% MeOH/CH2Cl2 gave the title compound as a white solid (14 mg). NMR (300 MHz, MeOH-d4) δ8.24 (broad s, 2H), 7.32 (broad s, 1H), 6.82 (d, J=8.25 Hz, 1H), 6.68-6.63 (m, 2H), 6.52 (t, J=4.76 Hz, 1H), 4.08 (t, J=6.11 Hz, 2H), 3.63 (d, J=5.59 Hz, 2H), 2.83 (dd, J=15.90, 3.70 Hz, 1H), 2.71 (d, J=3.32 Hz, 2H), 2.42-2.34 (m, 3H), 2.11 (dd, J=11.82, 5.88 Hz, 3H), 1.90 (d, J=11.76 Hz, 1H), 1.46-1.32 (m, 1H); MS (+ESI) m/z 342 (M+H)+; Calculated for C19H23N3O3.0.5 H2O: C, 64.94; H, 6.88; N, 11.96. Found: C, 65.43; H, 6.72; N, 11.48.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionWater was added to the residue
  4. temperaturethe mixture was cooled in an ice bath
  5. additionThe mixture was brought to pH 5 by the addition of 1N HCl
  6. extractionThe aqueous suspension was extracted with CH2Cl2 and CHCl3
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified
  12. washElution with 10% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-3f8daa0d7fa645c7ac74111239738f0b
Source dataset
uspto-grants-2002_08
Patent number
US06429214B1

Reaction notes

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