Ethanol → 8-(2-Chlorophenyl)-2,2 dimethyl-8-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-octanoic acid

HRID 1801537Notes

Reaction equation

HRID 1801537 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[NH: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[NH: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 569716038-(2-Chlorophenyl)-2,2 dimethyl-8-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-octanoic acid ethyl ester

Product 1

HCID 569716028-(2-Chlorophenyl)-2,2 dimethyl-8-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-octanoic acidYield 59.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
96.5 °C

Procedure

8-(2-Chlorophenyl)-2,2 dimethyl-8-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-octanoic acid ethyl ester (0.11 g, 0.25 mmol) was added to a mixture of ethanol (15 mL), water (1.35 mL), and sodium hydroxide (0.07 g, 1.75 mmol). The mixture was heated to reflux (95-98° C. oil bath) for 11 hours. After cooling to room temperature, the solvent was evaporated under reduced pressure. Water (10 mL) was added to the residue and adjusted to pH=6 with 10 N hydrochloric acid. The product was extracted with dichloromethane (3×10 mL). The combined organic layers were washed with water (10 mL), brine (10 mL), dried over Na2SO4. After filtration, the dichloromethane solution was concentrated under reduced pressure to obtain crude product. The crude product was purified by column chromatography (silica gel, ethyl acetate/heptane=3/7) to afford 8-(2-chlorophenyl)-2,2 dimethyl-8-(1,4,6,7-tetrahydro-pyrrolo[3,2-c]pyridine-5-yl)-octanoic acid (Compound Iq, 0.06 g, 59.8% yield) as a yellow oil. 1NMR (Field: 300 MHz, Solvent: CD3OD/TMS) δ (ppm): 7.60 (d, 1H, J=7.5 Hz), 7.48 (d, 1H, J=7.8 Hz), 7.41-7.30 (m, 2H), 6.58 (d, 1H, J=2.7 Hz), 5.89 (d, 1H, J=2.7 Hz), 4.56-4.52 (m, 1H), 3.96 (d, 1H, J=13.5 Hz), 3.65 (d, 1H, J=13.5 Hz), 2.97-2.65 (m, 4H), 2.00-1.87 (m, 2H), 1.43-1.39 (m, 2H), 1.28-1.18 (m, 6H), 1.11 (s, 6H). 13C NMR (Field: 75 MHz, Solvent: CD3OD/TMS) δ (ppm) 183.09, 136.97, 136.77, 131.03, 130.05, 130.31, 128.80, 124.29, 118.35, 113.24, 105.71, 65.49, 50.79, 49.81, 43.48, 42.01, 33.13, 30.39, 26.74, 26.19, 25.98, 23.34.

Workup

  1. temperatureThe mixture was heated
  2. temperatureAfter cooling to room temperature
  3. customthe solvent was evaporated under reduced pressure
  4. additionWater (10 mL) was added to the residue
  5. extractionThe product was extracted with dichloromethane (3×10 mL)
  6. washThe combined organic layers were washed with water (10 mL), brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationAfter filtration
  9. concentrationthe dichloromethane solution was concentrated under reduced pressure
  10. customto obtain crude product
  11. customThe crude product was purified by column chromatography (silica gel, ethyl acetate/heptane=3/7)

Sources & evidence

ORD record
ord-89c41ea06a014d4bbd09a6bb4bde9266
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

Loading…