Hydrochloric Acid → (2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(cycloheptylidene)methyl]phenyl}-2-propenoic acid

HRID 2100117Notes

Reaction equation

HRID 2100117 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:9](=[C:23]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[C:10]2[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([O:20]CC)=[O:19])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[OH:8].[OH-].[Na+].Cl>CCO.C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:9](=[C:23]2[CH2:29][CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[C:10]2[CH:15]=[CH:14][C:13](/[CH:16]=[CH:17]/[C:18]([OH:20])=[O:19])=[CH:12][CH:11]=2)[CH:5]=[CH:6][C:7]=1[OH:8]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 68975839Ethyl(2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(cycloheptylidene)methyl]phenyl}-2-propenoate

Product 1

HCID 11485398(2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(cycloheptylidene)methyl]phenyl}-2-propenoic acidYield 84%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of ethyl(2E)-3-{4-[(3-fluoro-4-hydroxyphenyl)(cycloheptylidene)methyl]phenyl}-2-propenoate (134) (0.22 g, 0.56 mmol) in a mixture of EtOH (6 mL) and THF (6 mL) was added an aqueous solution of 1 N NaOH (7 mL). The mixture was stirred at 60° C. for 2 h. Upon cooling, the mixture was acidified to pH=2 with an aqueous solution of 2 N HCl. The mixture was extracted with EtOAc (2×50 mL). The combined organic extract washed with brine and dried over Na2SO4. Upon concentration, light brown foam was obtained. It was triturated with hexanes (contains 1% MeOH) to give compound 135 as a pale yellow solid (0.171 g, 84%). mp 164-165° C. 1H NMR (400 MHz, DMSO-d6): δ 1.51 (br s, 8H), 2.10-2.30 (m, 4H), 6.45 (d, J=15.9 Hz, 1H), 6.70-6.78 (m, 1H), 6.80-6.90 (m, 1H), 7.14 (d, J=8.2 Hz, 2H), 7.53 (d, J=16.2 Hz, 1H), 7.59 (d, J=8.0 Hz, 2H), 9.74 (s, 1H), 12.35 (s, 1H). LCMS (ES): m/z 367 (M+H)+, m/z 365 (M−H)−. Anal. Calcd for C23H23FO3. 0.1H2O: C, 75.02; H, 6.35; Found: C, 74.93; H, 6.44.

Workup

  1. temperatureUpon cooling
  2. extractionThe mixture was extracted with EtOAc (2×50 mL)
  3. extractionThe combined organic extract
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationUpon concentration
  7. customlight brown foam was obtained
  8. customIt was triturated with hexanes (contains 1% MeOH)

Sources & evidence

ORD record
ord-2f3a047219134689813c155f4b6560c4
Source dataset
uspto-grants-2009_08
Patent number
US07569601B2

Reaction notes

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