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

HRID 576244
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HRID 576244 반응식
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]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

10

반응물 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

생성물 1

HCID 25145597
7-(2-Methoxyphenyl)-3-(3-((2-methyl-1-naphthyl)oxy)propyl)-1h-indole-2-carboxylic acid

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-dc8fe8a8f0c8490aae620907f860a853
출처 데이터셋
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09035047B2

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