Ethylene Glycol → 2-(4-(4-methyl-6-((tetrahydro-2H-pyran-2-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2H-chromen-2-yl)phenoxy)ethanol

HRID 717496Notes

Reaction equation

HRID 717496 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:17]([C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH:25]4[CH2:30][CH2:29][CH2:28][CH2:27][O:26]4)[CH:19]=3)=[C:16]([CH3:31])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([O:32][CH:33]4[CH2:38][CH2:37][CH2:36][CH2:35][O:34]4)[CH:14]=3)[O:9]2)=[CH:4][CH:3]=1.[CH2:39]([OH:42])[CH2:40][OH:41].N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C(=O)([O-])[O-].[K+].[K+]>C(#N)CCC.[Cu](I)I>[CH3:31][C:16]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:32][CH:33]3[CH2:38][CH2:37][CH2:36][CH2:35][O:34]3)[CH:14]=2)[O:9][CH:8]([C:5]2[CH:6]=[CH:7][C:2]([O:41][CH2:40][CH2:39][OH:42])=[CH:3][CH:4]=2)[C:17]=1[C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][O:26]2)[CH:19]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 866828852-(4-iodophenyl)-4-methyl-6-((tetrahydro-2H-pyran-2-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2H-chromene2×

Product 1

HCID 896202212-(4-(4-methyl-6-((tetrahydro-2H-pyran-2-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2H-chromen-2-yl)phenoxy)ethanol

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 8008ButyronitrileSolvent

Conditions

Temperature
125 °C

Procedure

A mixture of 2-(4-iodophenyl)-4-methyl-6-((tetrahydro-2H-pyran-2-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2H-chromene (Intermediate 3, 1.0 g, 1.6 mmol), ethane-1,2-diol (0.49 g, 8.0 mmol), copper iodide (0.03 g, 0.16 mmol), 1,10-phenanthroline (0.058 g, 0.32 mmol), potassium carbonate (0.44 g, 3.2 mmol) in butyronitrile (3.2 mL) was degassed three times via nitrogen/vacuum cycles. The reaction mixture was heated at 125° C. for 2 days, allowed to cool to room temperature, and diluted with ethyl acetate. This mixture was filtered through Celite. The organic phase was washed twice with water, washed with brine, dried over Na2SO4, filtered, and concentrated to afford the crude product. This crude product was then purified by silica gel chromatography to give 2-(4-(4-methyl-6-((tetrahydro-2H-pyran-2-yl)oxy)-3-(3-((tetrahydro-2H-pyran-2-yl)oxy)phenyl)-2H-chromen-2-yl)phenoxy)ethanol. 1H NMR (DMSO-d6): δ 7.27-7.13 (m, 3H), 6.98 (t, 1H), 6.93-6.84 (m, 3H), 6.80-6.76 (m, 3H), 6.59 (d, 1H), 5.97 (d, 1H), 5.43 (dt, 1H), 5.34 (br, 1H), 4.79 (t, 1H), 3.88 (t, 2H), 3.80-3.70 (m, 2H), 3.64 (q, 2H), 3.54-3.50 (m, 2H), 2.06 (s, 3H), 1.86-1.66 (m, 6H), 1.59-1.51 (m, 6H).

Workup

  1. customwas degassed three times via nitrogen/vacuum cycles
  2. temperatureto cool to room temperature
  3. additiondiluted with ethyl acetate
  4. filtrationThis mixture was filtered through Celite
  5. washThe organic phase was washed twice with water
  6. washwashed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customto afford the crude product
  11. customThis crude product was then purified by silica gel chromatography

Sources & evidence

ORD record
ord-eebfa5f34cac4fff938d51f22df03ef0
Source dataset
uspto-grants-2015_11
Patent number
US09193714B2

Reaction notes

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