Ethanol → HCID 131730141, compound

HRID 1801517Notes

Reaction equation

HRID 1801517 reaction equation
C([O:3][C:4](=[O:27])[C:5]([CH3:26])([CH3:25])[CH2:6][CH2:7][CH:8]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=1[Cl:24])[N:9]1[CH2:14][CH2:13][C:12]2[S:15][CH:16]=[CH:17][C:11]=2[CH2:10]1)C.C(O)C.[OH-].[K+]>O>[ClH:24].[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[CH:8]([N:9]1[CH2:14][CH2:13][C:12]2[S:15][CH:16]=[CH:17][C:11]=2[CH2:10]1)[CH2:7][CH2:6][C:5]([CH3:25])([CH3:26])[C:4]([OH:27])=[O:3]

Participants

5

Reactant 3

HCID 702EthanolHCID 14797Potassium HydroxideHCID 56971146HCID 56971146, compound

Product 1

HCID 131730141HCID 131730141, compoundYield 139.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

5-(2-Chlorophenyl)-5-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethylpentanoic acid ethyl ester (1.0 g, 2.46 mmol) was dissolved in water (5 mL) and ethanol (5 mL) that contained potassium hydroxide (1 g). The mixture was heated to reflux for 6 hours. After cooling to room temperature, the ethanol was removed under reduced pressure. Water (25 mL) was added and the solution was acidified to pH=5 to 6 with concentrated hydrochloric acid. The product was extracted with dichloromethane (2×25 mL). The combined dichloromethane extracts were dried over sodium sulfate, filtered, and concentrated. The crude product (1.06 g) was purified by column chromatography on silica gel (20 g), eluting with heptane/ethyl acetate (1:1). The product containing fractions were combined, concentrated, and dissolved in dichloromethane (25 mL). The dichloromethane solution was acidified with hydrochloric acid (2N) in diethyl ether (6 mL). The solvents were removed under reduced pressure. The remaining solid was dried to a constant weight at room temperature under high vacuum to provide 5-(2-chlorophenyl)-5-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)-2,2-dimethylpentanoic acid, hydrochloride salt (Compound Ia hydrochloride, 0.71 g, 69.6% yield) as a off-white solid. 1H NMR (300 MHz, DMS-d6/TMS): δ=12.20 (br s, 1H), 11.83 (br s, 0.5H), 11.61 (br s, 0.5H), 8.10 (m, 1H), 7.77-7.41 (m, 4H), 6.97 (d, 1H, J=4.5 Hz), 6.81 (d, 1H, J=4.5 Hz), 4.90-4.70 (m, 1.5H), 4.42-4.37 (m, 0.5H), 4.11-4.01 (m, 1H), 3.90-3.80 (m, 0.5H), 3.51 (m, 0.5H), 3.20-2.84 (m, 2H), 2.37 (m, 1H), 2.14 (m, 1H), 1.28 (m, 1H), 1.04 (s, 3H), 1.02 (s, 3H), 0.90 (m, 1H). (mixture of rotational isomers). 13C NMR (75 MHz, DMS-d6/TMS): δ=177.64, 134.50, 131.23, 130.89, 129.72, 129.38, 128.02, 127.33, 125.06, 124.68, 64.62, 63.52, 54.63, 49.73, 48.54, 47.93, 47.20, 40.72, 35.21, 25.90 (d), 24.78, 24.37, 21.79, 21.31 (d), 14.99. MS (MMI-TOF): Calculated for C20H25NO2Cl2S (MH+): 378.1289, found 378.1271. CHN analysis: Calculated; 57.97 C, 6.08 H, 3.38 N, 17.11 Cl, found; 56.07 C, 6.25 H, 3.12 N, 18.55 Cl, Best Fit for CHN Data: C20H25Cl2NO2S+0.65 H2O+0.05 HCl

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 6 hours
  3. customthe ethanol was removed under reduced pressure
  4. additionWater (25 mL) was added
  5. extractionThe product was extracted with dichloromethane (2×25 mL)
  6. dry with materialThe combined dichloromethane extracts were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product (1.06 g) was purified by column chromatography on silica gel (20 g)
  10. washeluting with heptane/ethyl acetate (1:1)
  11. additionThe product containing fractions
  12. concentrationconcentrated
  13. dissolutiondissolved in dichloromethane (25 mL)
  14. customThe solvents were removed under reduced pressure
  15. customThe remaining solid was dried to a constant weight at room temperature under high vacuum

Sources & evidence

ORD record
ord-590e865b5b354c468435207d969da88f
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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