Hydrochloric Acid → 2-(4-((2-(Cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetic acid

HRID 1508904Notes

Reaction equation

HRID 1508904 reaction equation
[CH:1]1([O:6][C:7]2[N:12]=[C:11]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([O:23]C)=[O:22])=[CH:16][CH:15]=3)[CH:10]=[C:9]([C:25]([F:28])([F:27])[F:26])[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.O1CCOCC1.O.[OH-].[Li+].Cl>C(OCC)(=O)C.O>[CH:1]1([O:6][C:7]2[N:12]=[C:11]([CH2:13][C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21]([OH:23])=[O:22])=[CH:16][CH:15]=3)[CH:10]=[C:9]([C:25]([F:27])([F:28])[F:26])[N:8]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 168937Lithium hydroxide, monohydrateHCID 90111569Methyl 2-(4-((2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetate

Product 1

HCID 901129182-(4-((2-(Cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetic acidYield 53.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

An 100-mL round bottom flask was charged with methyl 2-(4-((2-(cyclopentyloxy)-6-(trifluoromethyl)pyrimidin-4-yl)methyl)phenyl)acetate (0.100 g, 0.25 mmol), dioxane (6 ml) and water (3 ml). To this solution was then added lithium hydroxide monohydrate (0.053 g, 1.26 mmol). The resulting mixture was stirred at 50° C. for 1.5 h. The cooled reaction mixture was treated with 2N aqueous HCl until pH˜5, then diluted with ethyl acetate (75 mL). The organic layer was washed with saturated sodium chloride (5 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica using hexane/ethyl acetate (10:0 to 0:10) as the eluent, followed by preparative HPLC (water/acetonitrile with 0.05% TFA) to afford the title compound (0.051 g, 53%) as an off-white solid. MW=380.36. M.p. 97-99° C. 1H NMR (DMSO-d6, 500 MHz) δ 12.28 (br s, 1H), 7.52 (s, 1H), 7.28 (d, J=8.0 Hz, 2H), 7.20 (d, J=8.0 Hz, 2H), 5.35 (septet, J=3.0 Hz, 1H), 4.11 (s, 2H), 3.52 (s, 2H), 2.00-1.89 (m, 2H), 1.77-1.65 (m, 4H), 1.65-1.55 (m, 2H); APCI MS m/z 381 [M+H]+.

Workup

  1. customThe cooled reaction mixture
  2. washThe organic layer was washed with saturated sodium chloride (5 mL)
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-790929acaf6d4d8ba75f36bea0b36cd2
Source dataset
uspto-grants-2015_12
Patent number
US09221843B2

Reaction notes

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