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

HRID 2199713

反応式

HRID 2199713 の反応式
[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

参加物

10

反応物 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

生成物 1

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

試薬・触媒・溶媒 4

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 887Methanol溶媒HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-27c29fb767fd46948a778d63913fed73
出典データセット
uspto-grants-2016_06
特許番号
US09359296B2

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