Ethanol → 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid

HRID 1801533Notes

Reaction equation

HRID 1801533 reaction equation
C([O:3][C:4](=[O:30])[C:5]([CH3:29])([CH3:28])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])[N:12]1[CH2:17][CH2:16][C:15]2[O:18][CH:19]=[CH:20][C:14]=2[CH2:13]1)C.C(O)C.[OH-].[Na+]>O>[Cl:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[CH:11]([N:12]1[CH2:17][CH2:16][C:15]2[O:18][CH:19]=[CH:20][C:14]=2[CH2:13]1)[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][C:5]([CH3:29])([CH3:28])[C:4]([OH:30])=[O:3]

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 569716018-(2-chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester

Product 1

HCID 569716008-(2-chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acidYield 53.4%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

8-(2-Chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester (0.5 g, 1.16 mmol) was added to a mixture of ethanol (20 mL) and sodium hydroxide (0.32 g, 8.0 mmol) in water (6.6 mL). The mixture was heated to reflux for 6.5 hours. Evaporated solvent under reduced pressure and water (20 mL) was added to the residue. The aqueous solution was washed with a mixture of ethyl acetate/heptane 1/10 (10 mL), and the extract was discarded. The aqueous fraction was acidified with concentrated hydrochloric acid to pH=6 and the product was extracted with dichloromethane (3×20 mL). The combined dichloromethane extracts were dried over sodium sulfate, filtered, and concentrated under reduced pressure to provide 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid (0.25 g, 46.9%) as a yellow oil. The material was dissolved in diethyl ether (5 mL) and added to hydrochloric acid solution (2N HCl in diethyl ether, 0.34 mL). Water (12 mL) was added and after mixing the aqueous portion was separated and freeze dried to provide 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid, hydrochloride salt (Compound Io hydrochloride, 0.16 g, light yellow powder, 59.3% yield). 1H NMR (Field: 300 MHz, Solvent: CD3OD/TMS) δ (ppm): 7.77 (br s, 1H), 7.63-7.48 (m, 5H), 6.37 (br s, 1H), 5.05 (m, 1H), 4.18 (m, 1H), 3.62 (m, 1H), 3.02 (m, 2H), 2.36-2.24 (m, 2H), 1.42-1.40 (m, 2H), 1.32 (m, 2H), 1.20-1.18 (m, 4H), 1.11 (s, 6H), 1.08-0.92 (m, 1H). 13C NMR (Field: 75 MHz, Solvent: CD3OD/TMS) δ (ppm): 181.70, 147.11, 144.55, 137.40, 132.15, 131.89, 130.08, 128.21, 129.87, 112.37, 109.71, 66.34, 52.10, 50.05, 43.07, 41.60, 35.10, 31.67, 30.56, 26.64, 25.85, 22.31. HRMS (HR, DIP-CI): Calculated for C23H30ClNO3 (M+H)+: 404.1987, found 404.2009. CHN analysis: Calculated; 62.73 C, 7.09 H, 3.18 N, 16.10 Cl, found; 59.13 C, 7.04 H, 3.03 N, 13.58 Cl.

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 6.5 hours
  3. washThe aqueous solution was washed with a mixture of ethyl acetate/heptane 1/10 (10 mL)
  4. extractionthe product was extracted with dichloromethane (3×20 mL)
  5. dry with materialThe combined dichloromethane extracts were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-57741011446b4afbb363ce5a78b855b6
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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