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

HRID 1801532Notes

Reaction equation

HRID 1801532 reaction equation
[O:1]1[C:9]2[CH2:8][CH2:7][NH:6][CH2:5][C:4]=2[CH:3]=[CH:2]1.[CH2:10]([O:12][C:13](=[O:31])[C:14]([CH3:30])([CH3:29])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])[CH3:11].C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH2:10]([O:12][C:13](=[O:31])[C:14]([CH3:30])([CH3:29])[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH:20]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[Cl:27])[N:6]1[CH2:7][CH2:8][C:9]2[O:1][CH:2]=[CH:3][C:4]=2[CH2:5]1)[CH3:11]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 152899484,5,6,7-Tetrahydrofuro[3,2-C]pyridineHCID 675129798-Bromo-8-(2-chlorophenyl)-2,2-dimethyloctanoic acid ethyl ester

Product 1

HCID 569716018-(2-chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl esterYield 30.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

4,5,6,7-Tetrahydrofuro[3,2-c]pyridine (0.47 g, 3.82 mmol), 8-bromo-8-(2-chlorophenyl)-2,2-dimethyloctanoic acid ethyl ester (1.47 g, 3.78 mmol) in DMF (36 mL), and potassium carbonate (0.77 g, 5.58 mmol) were combined under an argon atmosphere at room temperature. The mixture was heated to 60° C. for 3 days under argon atmosphere, monitored by TLC. The DMF was evaporated under reduced pressure and the residue was dissolved in diethyl ether (120 mL), washed with water (3×30 mL), brine (30 mL), and dried over Na2SO4. The crude oil was purified by column chromatography (silica gel, ethyl acetate/heptane 1/9) to afford pure 8-(2-chlorophenyl)-8-(6,7-dihydro-4H-furo[3,2-c]pyridin-5-yl)-2,2-dimethyloctanoic acid ethyl ester (Compound Ip, 0.50 g, 30.3% yield) as a yellow oil. 1H NMR (Field: 300 MHz, Solvent: CD3OD/TMS) δ (ppm): 7.48 (d, 1H, J=7.5 Hz), 7.36 (d, 1H, J=7.8 Hz), 7.32-7.15 (m, 3H), 6.17 (s, 1H), 4.20 (dd, 1H, J=9.0, 4.8 Hz), 4.08 (q, 2H, J=7.2 Hz), 3.62 (d, 1H, J=13.5 Hz), 3.11 (d, 1H, J=13.5 Hz), 2.88-2.58 (m, 4H), 1.95-1.70 (m, 2H), 1.45-1.40 (m, 2H), 1.30-1.0 (m, 15H). 13C NMR (Field: 75 MHz, Solvent: CDCl3/TMS) δ (ppm): 178.01, 149.01, 140.94, 139.50, 135.00, 129.57, 129.04, 128.03, 126.85, 115.92, 108.90, 63.43, 60.36, 47.65, 47.54, 42.36, 40.91, 33.27, 30.57, 25.67, 25.41, 25.06, 24.73, 14.55. HRMS (HR, DART-TOF): Calculated for (M+H)+: 432.2300, found 432.2316.

Workup

  1. customwere combined under an argon atmosphere at room temperature
  2. customThe DMF was evaporated under reduced pressure
  3. dissolutionthe residue was dissolved in diethyl ether (120 mL)
  4. washwashed with water (3×30 mL), brine (30 mL)
  5. dry with materialdried over Na2SO4
  6. customThe crude oil was purified by column chromatography (silica gel, ethyl acetate/heptane 1/9)

Sources & evidence

ORD record
ord-65d8307905544ed4bf6bf08848e51dd3
Source dataset
uspto-grants-2013_01
Patent number
US08349833B2

Reaction notes

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