Thiazolidinedione → 6-[3-(1-Adamantyl)-4-methoxyphenyl]-naphthalen-2-yl-methyl-2,4-thiazolidinedione

HRID 860545Notes

Reaction equation

HRID 860545 reaction equation
[S:1]1[CH2:5][C:4](=[O:6])[NH:3][C:2]1=[O:7].[Li][CH2:9]CCC.[C:13]12([C:23]3[CH:24]=[C:25]([C:31]4[CH:32]=[C:33]5[C:38](=[CH:39][CH:40]=4)[CH:37]=[C:36](CI)[CH:35]=[CH:34]5)[CH:26]=[CH:27][C:28]=3[O:29][CH3:30])[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2>C1COCC1.O>[C:13]12([C:23]3[CH:24]=[C:25]([C:31]4[CH:32]=[C:33]5[C:38](=[CH:39][CH:40]=4)[CH:37]=[C:36]([CH:5]4[S:1][C:2](=[O:7])[N:3]([CH3:9])[C:4]4=[O:6])[CH:35]=[CH:34]5)[CH:26]=[CH:27][C:28]=3[O:29][CH3:30])[CH2:22][CH:17]3[CH2:18][CH:19]([CH2:21][CH:15]([CH2:16]3)[CH2:14]1)[CH2:20]2

Participants

6

Reactant 3

HCID 5437ThiazolidinedioneHCID 695838266-[3-(1-Adamantyl)-4-methoxyphenyl]-naphthalen-2-yl-methyliodideHCID 178418339Butyllithium

Product 1

HCID 878990396-[3-(1-Adamantyl)-4-methoxyphenyl]-naphthalen-2-yl-methyl-2,4-thiazolidinedioneYield 56%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 2,4-thiazolidinedione (0.094 g, 0.80 mmol) in 4.0 mL of anhydrous THF at −78° C. under argon was added n-BuLi (0.58 mL of 2.5 M in hexanes). After 20 minutes, the reaction mixture was allowed to warm to 0° C. for 30 minutes then cooled to −78° C. To this mixture was added 6-[3-(1-adamantyl)-4-methoxyphenyl]-naphthalen-2-yl-methyliodide (0.177 g, 0.35 mmol) in 3 mL anhydrous THF and stirred at −78° C. for 30 minutes. The reaction mixture was warmed to room temperature. After 14 hours, the reaction mixture was diluted with water and extracted with EtOAc (2×50 mL). The combined organics were washed with water (100 mL), sat. NH4Cl (100 mL), brine (100 mL), dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified on silica gel (eluent: hexane:EtOAc 4:1) to give 0.097 g of 6-[3-(1-adamantyl)-4-methoxyphenyl]-naphthalen-2-yl-methyl-2,4-thiazolidinedione (56%), mp 251–253° C. 1H NMR (300 MHz; DMSO-d6): δ 1.80 (brs, 6H), 2.10–2.18 (m, 9H), 3.32 (dd, J=9.6 Hz, J=14.1 Hz, 1H), 3.72 (dd, J=3.6 Hz, J=14.1 Hz, 1H), 3.90 (s, 3H), 4.65 (dd, J=3.6 Hz, J=9.9 Hz, 1H), 6.99 (d, J=8.1 Hz, 1H), 7.36 (dd, J=1.5 Hz, J=8.4 Hz, 1H), 7.52 (dd, J=1.8 Hz, J=8.7 Hz, 1H), 7.57 (d, J=2.1 Hz, 1H), 7.70–7.76 (m, 2H), 7.84 (d, J=3.3 Hz, 1H), 7.87 (d, J=3.6 Hz, 1H), 7.96 (d, J=0.3 Hz, 1H), 8.13 (brs, 1H). 13C NMR (75 MHz; DMSO-d6): 38.4, 46.6, 47.4, 62.7, 65.3, 122.6, 134.0, 134.7, 135.3, 137.3, 137.6, 137.9, 138.1, 141.5, 141.8, 142.3, 144.1, 147.7, 147.8, 168.1, 181.4, 185.5.

Workup

  1. temperaturethen cooled to −78° C
  2. temperatureThe reaction mixture was warmed to room temperature
  3. waitAfter 14 hours
  4. extractionextracted with EtOAc (2×50 mL)
  5. washThe combined organics were washed with water (100 mL), sat. NH4Cl (100 mL), brine (100 mL)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified on silica gel (eluent: hexane:EtOAc 4:1)

Sources & evidence

ORD record
ord-b61002707b154dcab053bcca8fecd52c
Source dataset
uspto-grants-2006_12
Patent number
US07153875B2

Reaction notes

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