Hydrochloric Acid → 7-(4-Hydroxy-2-methylphenyl)-3-(3-(1-naphthyloxy)propyl)-1h-indole-2-carboxylic acid

HRID 576242

반응식

HRID 576242 반응식
[C:1]1([O:11][CH2:12][CH2:13][CH2:14][C:15]2[C:23]3[C:18](=[C:19](B4OC(C)(C)C(C)(C)O4)[CH:20]=[CH:21][CH:22]=3)[NH:17][C:16]=2[C:33]([O:35]CC)=[O:34])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.Br[C:39]1[CH:44]=[CH:43][C:42]([OH:45])=[CH:41][C:40]=1[CH3:46].F[B-](F)(F)F.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[Li+].[OH-].Cl>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.CO>[OH:45][C:42]1[CH:43]=[CH:44][C:39]([C:19]2[CH:20]=[CH:21][CH:22]=[C:23]3[C:18]=2[NH:17][C:16]([C:33]([OH:35])=[O:34])=[C:15]3[CH2:14][CH2:13][CH2:12][O:11][C:1]2[C:10]3[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=3)[CH:4]=[CH:3][CH:2]=2)=[C:40]([CH3:46])[CH:41]=1

참가 물질

10

반응물 5

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 728574-Bromo-m-cresolHCID 44558591Tri-t-butylphosphine fluoroborateHCID 68940461Ethyl 3-(3-(naphthalen-1-yloxy)propyl)-7-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1h-indole-2-carboxylate

생성물 1

HCID 689436107-(4-Hydroxy-2-methylphenyl)-3-(3-(1-naphthyloxy)propyl)-1h-indole-2-carboxylic acid

시약·촉매·용매 4

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 887Methanol용매HCID 962Water용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a mixture of EXAMPLE 43A (50 mg) and 4-bromo-3-methylphenol (22 mg) in THF (2 mL) was added tris(dibenzylideneacetone)dipalladium(0) (4.6 mg), and tri-tert-butylphosphine tetrafluoroborate (1.45 mg). The mixture was stirred at ambient temperature overnight and partitioned between ethyl acetate (150 mL) and water (50 mL). The extract was washed with brine, dried over sodium sulfate, and filtered. The filtrate was concentrated, and the concentrate was loaded on a silica gel cartridge and eluted with ethyl acetate (5%) in hexanes to provide a product 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% aqueous HCl and extracted with ethyl acetate. The exteact was washed with water and brine and dried (Na2SO4), filtered and concentrated. The concentrate was purified by reverse phase HPLC as described in Example 1D. 1H NMR (300 MHz, CDCl3) δ 8.39 (d, 1H), 8.35 (d, 1H), 7.77 (d, 1H), 7.72 (dd, 1H), 7.13-7.50 (m, 6H), 6.85 (d, 1H), 6.76 (t, 2H), 4.21 (t, 2H), 3.47 (t, 2H), 2.38 (m, 2H), 2.13 (s, 3H).

후처리

  1. custompartitioned between ethyl acetate (150 mL) and water (50 mL)
  2. washThe extract was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated
  6. washeluted with ethyl acetate (5%) in hexanes
  7. customto provide a product which
  8. extractionextracted with ethyl acetate
  9. washThe exteact was washed with water and brine
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe concentrate was purified by reverse phase HPLC

출처 및 근거

ORD 기록
ord-b3dcca291c0a41fca6c3662a611149bf
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09035047B2

연결된 노트

불러오는 중…