Water → HCID 60147146, compound

HRID 2113183Notes

Reaction equation

HRID 2113183 reaction equation
[CH2:1]([C:8]1[O:9][C:10]2[CH:41]=[CH:40][CH:39]=[CH:38][C:11]=2[C:12]=1[C:13]1[CH:37]=[CH:36][C:16]([C:17]2[CH:22]=[CH:21][C:20]([C:23](=[O:35])[CH2:24][CH:25]3[C:30](=[O:31])[O:29][C:28]([CH3:33])([CH3:32])[O:27][C:26]3=[O:34])=[CH:19][CH:18]=2)=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[CH2:44](Br)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1.O>C1COCC1.CN(C=O)C.C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:44]([C:25]1([CH2:24][C:23]([C:20]2[CH:19]=[CH:18][C:17]([C:16]3[CH:15]=[CH:14][C:13]([C:12]4[C:11]5[CH:38]=[CH:39][CH:40]=[CH:41][C:10]=5[O:9][C:8]=4[CH2:1][C:2]4[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=4)=[CH:37][CH:36]=3)=[CH:22][CH:21]=2)=[O:35])[C:30](=[O:31])[O:29][C:28]([CH3:33])([CH3:32])[O:27][C:26]1=[O:34])[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

8

Reactant 4

HCID 962WaterHCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 60147144HCID 60147144, compound

Product 1

HCID 60147146HCID 60147146, compoundYield 89.4%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent2×HCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Procedure

A solution of 5-{2-[4′-(2-benzylbenzofuran-3-yl)-biphen-4-yl]-2-oxoethyl}-2,2-dimethyl-[1,3]dioxane-4,6-dione (200 mg, 0.37 mmol) in THF/DMF (5:1; 6 mL) was added dropwise to a stirred suspension of sodium hydride (95%, 10.2 mg, 0.40 mmol) in anhydrous THF (5 mL) at room temperature. The clear solution was stirred at room temperature for 30 mins and then a solution of benzyl bromide (76 mg, 0.44 mmol) in THF (5 mL) was added dropwise, followed by the addition of tetra-n-butylammonium iodide (5 mg) as a solid. The reaction mixture was warmed to 60° C. for 4 hrs (TLC control), cooled to room temperature and then water (10 mL) was added cautiously. The reaction mixture was extracted with diethyl ether (3×15 mL). The combined extract was washed with water (2×10 mL), brine (3×10 mL), dried over anhydrous MgSO4, filtered and concentrated in vacuo. Purification of the product by trituration and filtration from MeOH afforded the title compound as a pale yellow solid (210 mg). 1H-NMR (CDCl3, 300 MHz): δ 8.12 (2H, d, J=8 Hz, Ar-H), 7.88 (4H, d, J=6 Hz, Ar-H), 7.53-7.69 (4H, m, Ar-H), 7.26 (1H, m, Ar-H), 7.14 (11H, m, Ar-H), 4.26 (2H, s, PhCH2), 4.16 (2H, CH2CO), 3.38 (2H, s, PhCH2), 1.98 (3H, s, Me), 0.78 (3H, s, Me).

Workup

  1. temperatureThe reaction mixture was warmed to 60° C. for 4 hrs (TLC control)
  2. temperaturecooled to room temperature
  3. extractionThe reaction mixture was extracted with diethyl ether (3×15 mL)
  4. extractionThe combined extract
  5. washwas washed with water (2×10 mL), brine (3×10 mL)
  6. dry with materialdried over anhydrous MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification of the product
  10. filtrationby trituration and filtration from MeOH

Sources & evidence

ORD record
ord-81d39d0fbdad45608f665130a4aaa952
Source dataset
uspto-grants-2009_04
Patent number
US07524878B2

Reaction notes

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