Lithium Chloride → HCID 16114909, compound

HRID 603966Notes

Reaction equation

HRID 603966 reaction equation
[CH:1]([NH:14][C:15]1[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][C:16]=1I)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:25][O:26][C:27](=[O:42])[C:28]1[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][C:37]#[C:38][CH2:39][CH2:40][OH:41])=[CH:30][CH:29]=1.[Li+].[Cl-]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[CH3:25][O:26][C:27](=[O:42])[C:28]1[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][C:37]2[C:16]3[C:15](=[CH:20][CH:19]=[C:18]([N+:21]([O-:23])=[O:22])[CH:17]=3)[N:14]([CH:1]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)[C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[C:38]=2[CH2:39][CH2:40][OH:41])=[CH:32][CH:33]=1

Participants

6

Reactant 3

HCID 433294Lithium ChlorideHCID 16114908HCID 16114908, compoundHCID 16116214HCID 16116214, compound

Product 1

HCID 16114909HCID 16114909, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Benzhydryl-(4-nitro-2-iodo-phenyl)-amine (1 eq.), 4-(6-hydroxy-hex-3-ynyloxy)-benzoic acid methyl ester (1.5 eq.), LiCl (1 eq.) KOAc (5 eq.) and palladium (II) acetate (0.04 eq.) were added to a roundbottom containing 10 mL of DMF that had been degassed with argon. The reaction heated to 100° C. 7.5 hours. It was then cooled, diluted with ethyl acetate, washed with water and brine, dried over Na2SO4 and concentrated to give a brown solid. Purification by flash chromatography gave two products, 4-{2-[1-benzhydryl-5-nitro-2-(2-hydroxy-ethyl)-1H-indol-3-yl]-ethoxy}-benzoic acid methyl ester and the desired, 4-{2-[1-benzhydryl-5-nitro-3-(2-hydroxy-ethyl)-1H-indol-2-yl]-ethoxy}-benzoic acid methyl ester in an overall yield of 71%. The products were not separable by flash chromatography and were both carried on to the next step. 1H NMR (400 MHz, CDCl3) □ ppm 1.66 (t, J=5.56 Hz, 1H), 1.80 (t, J=5.18 Hz, 1H), 3.14 (m, 4H), 3.35 (m, 4H), 3.81 (m, 2H), 3.87 (m, J=1.52 Hz, 6H), 3.97 (q, J=6.32 Hz, 2H), 4.10 (t, J=6.82 Hz, 2H), 4.31 (t, J=6.19 Hz, 2H), 6.58 (d, J=4.04 Hz, 1H), 6.60 (d, J=4.04 Hz, 1H), 6.67 (d, J=9.10 Hz, 2H), 6.89 (d, J=8.84 Hz, 2H), 7.10 (m, 9H), 7.20 (s, 1H), 7.32 (m, 12H), 7.75 (m, 2H), 7.90 (d, J=8.84 Hz, 2H), 7.95 (d, J=9.09 Hz, 2H), 8.52 (d, J=2.27 Hz, 1H), 8.59 (d, J=2.27 Hz, 1H).

Workup

  1. customhad been degassed with argon
  2. custom7.5 hours
  3. temperatureIt was then cooled
  4. additiondiluted with ethyl acetate
  5. washwashed with water and brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customto give a brown solid
  9. customPurification by flash chromatography

Sources & evidence

ORD record
ord-0514386716c442439bdc30332fd82745
Source dataset
uspto-grants-2011_03
Patent number
US07906548B2

Reaction notes

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