Ethanol → 7-(2-Chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acid

HRID 1526465Notes

Reaction equation

HRID 1526465 reaction equation
C([O:3][C:4](=[O:29])[C:5]([CH3:28])([CH3:27])[CH2:6][CH2:7][CH2:8][CH2:9][CH:10]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=1[Cl:26])[N:11]1[CH2:16][CH2:15][C:14]2[NH:17][CH:18]=[CH:19][C:13]=2[CH2:12]1)C.C(O)C.[OH-].[Na+]>O>[Cl:26][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH:10]([N:11]1[CH2:16][CH2:15][C:14]2[NH:17][CH:18]=[CH:19][C:13]=2[CH2:12]1)[CH2:9][CH2:8][CH2:7][CH2:6][C:5]([CH3:28])([CH3:27])[C:4]([OH:29])=[O:3]

Participants

5

Reactant 3

HCID 702EthanolHCID 14798Sodium HydroxideHCID 569713857-(2-Chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acid ethyl ester

Product 1

HCID 569713847-(2-Chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acidYield 57.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
96.5 °C

Procedure

7-(2-Chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acid ethyl ester (0.21 g, 0.51 mmol) was added to a mixture of ethanol (10 mL), water (2.70 mL), and sodium hydroxide (0.14 g, 3.54 mmol). The mixture was heated to reflux (95-98° C. oil bath) for 16 hours. After 26 hours, the flask was cooled to room temperature and the solvent was evaporated under reduced pressure. Water (15 mL) was added to the residue and the product was extracted with diethyl ether (15 mL). The extract was discarded and the aqueous portion was adjusted pH=6 with 10 N hydrochloric acid. The product was extracted with dichloromethane (3×15 mL) and the combined dichloromethane layers were washed with water (20 mL) and brine (20 mL). The dichloromethane solution was dried over sodium sulfate, filtered, and concentrated in under reduced pressure. The crude product was purified by column chromatography (silica gel, MeOH/CH2Cl2=1/9) to afford 7-(2-chlorophenyl)-2,2 dimethyl-7-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-heptanoic acid (Compound Ik, 0.11 g, 57.9% yield) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: DMSO/TMS) δ (ppm): 12.10 (br, 1H), 10.30 (br, 1H), 7.53 (m, 1H), 7.43 (d, 1H, J=7.2 Hz), 7.36-7.25 (m, 2H), 6.50 (s, 1H), 5.71 (s, 1H), 4.10 (m, 1H), 3.39 (m, 5H), 2.75 (m, 1H), 1.14 (m, 2H), 1.34 (m, 2H), 1.23-1.07 (m, 4H), 1.03 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: DMSO/TMS) 6 (ppm) 178.45, 178.97, 133.83, 129.07, 128.23, 126.93, 123.97, 115.83, 113.99, 104.19, 63.11, 48.27, 47.60, 41.19, 40.06, 31.59, 25.84, 25.03, 24.96, 24.55, 23.34.

Workup

  1. temperatureThe mixture was heated
  2. temperaturethe flask was cooled to room temperature
  3. customthe solvent was evaporated under reduced pressure
  4. additionWater (15 mL) was added to the residue
  5. extractionthe product was extracted with diethyl ether (15 mL)
  6. extractionThe product was extracted with dichloromethane (3×15 mL)
  7. washthe combined dichloromethane layers were washed with water (20 mL) and brine (20 mL)
  8. dry with materialThe dichloromethane solution was dried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in under reduced pressure
  11. customThe crude product was purified by column chromatography (silica gel, MeOH/CH2Cl2=1/9)

Sources & evidence

ORD record
ord-bbcac6b7b0e2491f936656663d866a7a
Source dataset
uspto-grants-2015_07
Patent number
US09085585B2

Reaction notes

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