Ethanol → HCID 56971147, compound

HRID 1801521Notes

Reaction equation

HRID 1801521 reaction equation
C([O:3][C:4](=[O:28])[C:5]([CH3:27])([CH3:26])[CH2:6][CH2:7][CH2:8][CH:9]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=1[Cl:25])[N:10]1[CH2:15][CH2:14][C:13]2[S:16][CH:17]=[CH:18][C:12]=2[CH2:11]1)C.C(O)C.[OH-].[Na+]>O>[Cl:25][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][C:19]=1[CH:9]([N:10]1[CH2:15][CH2:14][C:13]2[S:16][CH:17]=[CH:18][C:12]=2[CH2:11]1)[CH2:8][CH2:7][CH2:6][C:5]([CH3:26])([CH3:27])[C:4]([OH:28])=[O:3]

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 56971149HCID 56971149, compound

Product 1

HCID 56971147HCID 56971147, compoundYield 68.7%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

6-(2-Chlorophenyl)-6-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5yl)-2,2-dimethylhexanoic acid ethyl ester (2.5 g, 7.33 mmol) was added to a solution of ethanol (100 mL) and sodium hydroxide (1.8 g, 43.8 mmol) in water (32 mL). The mixture was heated to reflux for 6.5 hours. The solution was evaporated under reduced pressure and water (100 mL) was added to the residue. The water solution was extracted with ethyl acetate/heptane=1/10 (100 mL). The organic layers were discarded and the aqueous solution was adjusted with 10 N hydrochloric acid solution to pH=6. The product was extracted with dichloromethane (3×100 mL), which was dried over Na2SO4, filtered, and concentrated under reduced pressure to provide 6-(2-chlorophenyl)-6-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5yl)-2,2-dimethylhexanoic acid (1.6 g, 68.7%) as a yellow oil. 6-(2-Chlorophenyl)-6-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5yl)-2,2-dimethylhexanoic acid (3.97 g, 10.2 mmol) was dissolved in 36% HCl (0.95 mL) and water (59 mL). After stirring for 10 minutes, the aqueous solution was extracted with ethyl acetate/heptane (20/80, 110 mL). The organic extract was discarded and the aqueous fraction was freeze-dried to provide 6-(2-chlorophenyl)-6-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5yl)-2,2-dimethylhexanoic acid, hydrochloride salt (Compound Ic hydrochloride, 3.48 g, 79.8% yield, 99.7% purity by HPLC) as a white solid melting at 136-138° C. 1H NMR (Field: 300 MHz, Solvent: CDCl3/TMS) δ (ppm): 7.69 (s, 1H), 7.47-7.38 (m, 3H), 7.21 (d, 1H, J=3.9 Hz), 6.71 (d, 1H, J=3.9 Hz), 4.92 (m, 1H), 4.31-4.15 (m, 2H), 3.15-3.05 (m, 4H), 2.24-2.14 (m, 2H), 1.47-1.36 (m, 2H), 1.08-1.06 (m, 2H), 0.99 (s, 6H). (mixture of rotation isomers in NMR). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 181.10, 137.13, 132.80, 132.77, 132.04, 131.79, 130.48, 129.73, 128.73, 126.62, 126.14, 66.14, 51.52, 42.87, 40.92, 32.04, 25.88, 25.47, 23.45, 22.50. MS (FIA-ESI-TOF): Calculated for C21H26ClNO2S (MH)+: 392.1446; found 392.1453. CHN analysis: Calculated; 58.87 C, 6.35 H, 3.27 N, 16.55 Cl, 7.48 S, found; 57.80 C, 6.44 H, 3.15 N, 16.14 Cl, 7.15 S, Best fit for CHN Data: C21H27Cl2NO2S+0.55 H2O

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 6.5 hours
  3. customThe solution was evaporated under reduced pressure and water (100 mL)
  4. additionwas added to the residue
  5. extractionThe water solution was extracted with ethyl acetate/heptane=1/10 (100 mL)
  6. extractionThe product was extracted with dichloromethane (3×100 mL), which
  7. dry with materialwas dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f5545b1d78024d9aaf2406acb31f2b5b
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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