Hydrochloric Acid → {2-Methyl-6-[3-(quinolin-2-ylmethoxy)-propoxvmethyl]-phenoxy}-acetic Acid

HRID 2117222Notes

Reaction equation

HRID 2117222 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][CH2:14][CH2:15][CH2:16][O:17][CH2:18][C:19]2[CH:28]=[CH:27][C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)N=2)[C:3]=1OCC#N.[OH-:29].[Na+].Cl.[NH4+:32].[Cl-].[C:34]([O:37]CC)(=[O:36])[CH3:35]>C(O)C>[CH3:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]([CH2:12][O:13][CH2:14][CH2:15][CH2:16][O:17][CH2:18][C:19]2[CH:28]=[CH:27][C:26]3[C:25](=[CH:24][CH:23]=[CH:22][CH:21]=3)[N:32]=2)[C:3]=1[O:29][CH2:35][C:34]([OH:37])=[O:36]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 14798Sodium HydroxideHCID 25517Ammonium ChlorideHCID 18008077HCID 18008077, compound

Product 1

HCID 20597844{2-Methyl-6-[3-(quinolin-2-ylmethoxy)-propoxvmethyl]-phenoxy}-acetic Acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

{2-Methyl-6-[3-(quinolin-2-ylmethoxy)-propoxymethyl]-phenoxy}-acetonitrile (333 mg, 0.89 mmol, EXAMPLE 6a) is dissolved in ethanol (8 mL). 10 N NaOH (900 μL, 9.0 mmol) is added and the contents heated to 60° C. for 2 hrs. The reaction is cooled to r.t. and the pH adjusted to ˜4 with 2 N HCl. The contents are partioned between aq. NH4Cl (10%, 100 mL) and ethyl acetate (100 mL). The aqueous layer is further extracted with ethyl acetate (2×75 mL). The organic fractions are combined and washed with sat. aq. NH4Cl (2×125 mL), dried over MgSO4, filtered and reduced under vacuum to an oil. The crude material is purified by flash chromatography (silica, 6% methanol in dichloromethane) to give the title compound. 1H NMR (300 MHz, CDCl3) δ 8.29-8.21 (m, 2H), 7.82 (d, 1H), 7.75 (t, 1H), 7.56 (dd, 1H), 7.50 (d, 1H), 7.15 (dd, 2H), 7.00 (dd, 1H), 4.79 (s, 2H), 4.61 (s, 2H), 4.55 (s, 2H), 3.70-3.47 (m, 4H), 2.31 (s, 3H), 1.95 (m, 2H). MS (ESI) 396 (M+H)+.

Workup

  1. temperatureThe reaction is cooled to r.t.
  2. extractionThe aqueous layer is further extracted with ethyl acetate (2×75 mL)
  3. washwashed with sat. aq. NH4Cl (2×125 mL)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customThe crude material is purified by flash chromatography (silica, 6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-1efe620dde4b47ba8e0489d099da3353
Source dataset
uspto-grants-2008_10
Patent number
USRE040558E1

Reaction notes

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