Hydrochloric Acid → 7-(2-Methoxyphenyl)-3-(3-((2-methyl-1-naphthyl)oxy)propyl)-1h-indole-2-carboxylic acid

HRID 2199715Notes

Reaction equation

HRID 2199715 reaction equation
O[CH2:2][CH2:3][CH2:4][C:5]1[C:13]2[C:8](=[C:9]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[O:20][CH3:21])[CH:10]=[CH:11][CH:12]=2)[NH:7][C:6]=1[C:22]([O:24]CC)=[O:23].[CH3:27][C:28]1[CH:37]=[CH:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:29]=1[OH:38].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O.[Li+].[OH-].Cl>C1COCC1.O.CO>[CH3:21][O:20][C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][C:14]=1[C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:8]=1[NH:7][C:6]([C:22]([OH:24])=[O:23])=[C:5]2[CH2:4][CH2:3][CH2:2][O:38][C:29]1[C:30]2[C:35](=[CH:34][CH:33]=[CH:32][CH:31]=2)[CH:36]=[CH:37][C:28]=1[CH3:27]

Participants

10

Reactant 6

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 11776TriphenylphosphineHCID 240552-Methyl-1-naphtholHCID 97268Di-tert-butyl azodicarboxylateHCID 68940496ethyl 3-(3-hydroxypropyl)-7-(2-methoxyphenyl)-1H-indole-2-carboxylate

Product 1

HCID 251455977-(2-Methoxyphenyl)-3-(3-((2-methyl-1-naphthyl)oxy)propyl)-1h-indole-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a mixture of EXAMPLE 47A (71 mg), 2-methyl-1-naphthol (35 mg), triphenylphosphine (58 mg) in THF (2 mL) and di-tert-butyl azodicarboxylate (55 mg) was stirred at ambient temperature overnight and partitioned between ethyl acetate (150 mL) and water (50 mL). The organic layer was washed with brine and a dried (Na2SO4), filtered and concentrated. The concentrate was purified by flash chromatography on silica gel with 5% ethyl acetate in hexanes to provide an intermediate which was dissolved in THF (2 mL), methanol (1 mL) and water (1 mL) and hydrolyzed with LiOH (100 mg) overnight. The mixture was acidified with 5% HCl and extracted with ethyl acetate. The extract was washed with water and brine and dried (Na2SO4), filtered and concentrated. The concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA). 1H NMR (300 MHz, CDCl3) δ 8.74 (s, 1H), 8.12 (dd, 1H), 7.82 (d, 1H), 7.77 (d, 1H), 7.52 (d, 1H), 7.36-7.47 (m, 5H), 7.27 (d, 1H), 7.09 (t, 2H), 4.10 (t, 2H), 3.83 (s, 3H), 3.48 (t, 2H), 2.46 (s, 3H), 2.38 (m, 2H).

Workup

  1. custompartitioned between ethyl acetate (150 mL) and water (50 mL)
  2. washThe organic layer was washed with brine
  3. dry with materiala dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe concentrate was purified by flash chromatography on silica gel with 5% ethyl acetate in hexanes
  7. customto provide an intermediate which
  8. extractionextracted with ethyl acetate
  9. washThe extract was washed with water and brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe concentrate was purified by reverse phase HPLC (C-18, 30 to 100% acetonitrile/water/0.1% TFA)

Sources & evidence

ORD record
ord-21079d3b32ea41b5880f01dae755380b
Source dataset
uspto-grants-2016_06
Patent number
US09359296B2

Reaction notes

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