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 717496노트

반응식

HRID 717496 반응식
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

참가 물질

7

반응물 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-chromene2회

생성물 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

시약·촉매·용매 2

HCID 83717Copper iodide촉매HCID 8008Butyronitrile용매

반응 조건

온도
125 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-eebfa5f34cac4fff938d51f22df03ef0
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193714B2

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