Cesium carbonate → (S)-2-{5-[2-(1,6-dibromo-naphthalen-2-yloxy)-ethoxy]-indol-1-yl}-propionic acid

HRID 734403Notes

Reaction equation

HRID 734403 reaction equation
[Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Br:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[O:13][CH2:14][CH2:15]Br.C[O:18][C:19](=[O:32])[CH:20]([N:22]1[C:30]2[C:25](=[CH:26][C:27]([OH:31])=[CH:28][CH:29]=2)[CH:24]=[CH:23]1)[CH3:21].C(=O)([O-])[O-].[Cs+].[Cs+].C([O-])(O)=O.[Na+]>CN(C=O)C>[Br:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Br:12])=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[O:13][CH2:14][CH2:15][O:31][C:27]1[CH:26]=[C:25]2[C:30](=[CH:29][CH:28]=1)[N:22]([C@@H:20]([CH3:21])[C:19]([OH:32])=[O:18])[CH:23]=[CH:24]2

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 516892Sodium BicarbonateHCID 57845447methyl 2-(5-hydroxy-1H-indol-1-yl)propanoateHCID 578454491,6-Dibromo-2-(2-bromoethoxy)naphthalene

Product 1

HCID 57845393(S)-2-{5-[2-(1,6-dibromo-naphthalen-2-yloxy)-ethoxy]-indol-1-yl}-propionic acid

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of 1,6-dibromo-2-(2-bromo-ethoxy)naphthalene (0.4 g, 0.98 mmol) (Example 15) in dry DMF (6 mL) was added 2-(5-hydroxy-indol-1-yl)-propionic acid methyl ester (0.215 g, 0.98 mmol) (Example 7) followed by cesium carbonate (1.59 g, 4.9 mmol). The reaction mixture was heated to 140° C. for 10 minutes and subsequently at 50° C. for 16 h. A saturated aqueous NaHCO3 solution was added and the reaction mixture was extracted with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated. The crude material was purified on reverse phase HPLC with gradient of 40% to 100% of acetonitrile and water mixture. The racemic mixture of the title compounds (122 mg, 46.3%) was collected as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 7.23-7.22(1H, m), 8.00-7.97 (2H, m), 7.71 (1H, dd), 7.63 (1H, d), 7.38 (1H, d), 7.29 (1H, d), 7.12 (1H, d), 6.79 (1H, dd), 6.36 (1H, d), 5.24 (1H, q), 4.58-4.55 (2H, m), 4.37-4.34 (2H, m), 1.68 (3H, d). LC/MS m/z 530 (M−H)−, RT 3.60 min

Workup

  1. extractionthe reaction mixture was extracted with ethyl acetate
  2. dry with materialThe combined organic layers were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe crude material was purified on reverse phase HPLC with gradient of 40% to 100% of acetonitrile and water mixture
  6. additionThe racemic mixture of the title compounds (122 mg, 46.3%)
  7. customwas collected as a white solid
  8. customLC/MS m/z 530 (M−H)−, RT 3.60 min

Sources & evidence

ORD record
ord-40e3a6c39b3a4f9c844384c75d0724d1
Source dataset
uspto-grants-2009_09
Patent number
US07592361B2

Reaction notes

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