Lithium diisopropylamide → tert-butyl 4-((6-cyanobenzofuran-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174090ノート

反応式

HRID 2174090 の反応式
[O:1]1[C:5]2[CH:6]=[C:7]([C:10]#[N:11])[CH:8]=[CH:9][C:4]=2[CH:3]=[CH:2]1.[Li+].CC([N-]C(C)C)C.[CH:20]([C:22]1[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]2[C:23]=1[CH:24]=[CH:25][N:26]2[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])=[O:21]>C1COCC1.CO.[NH4+].[Cl-].[Cl-].[Na+].O.CCOC(C)=O>[C:10]([C:7]1[CH:8]=[CH:9][C:4]2[CH:3]=[C:2]([CH:20]([OH:21])[C:22]3[C:30]([O:31][CH3:32])=[CH:29][C:28]([CH3:33])=[C:27]4[C:23]=3[CH:24]=[CH:25][N:26]4[C:34]([O:36][C:37]([CH3:39])([CH3:38])[CH3:40])=[O:35])[O:1][C:5]=2[CH:6]=1)#[N:11]

参加物

9

反応物 3

HCID 2724682Lithium diisopropylamideHCID 212514851-Benzofuran-6-carbonitrileHCID 72191522tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate

生成物 1

HCID 86701726tert-butyl 4-((6-cyanobenzofuran-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

試薬・触媒・溶媒 5

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 25517Ammonium Chloride溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

To a solution of benzofuran-6-carbonitrile (CAS #: 17450-68-9) (29.7 mg, 0.207 mmol) in THF (1.7 mL), 1.8M LDA (heptane/THF/ethylbenzene, 0.125 mL, 0.225 mmol) was added at −78° C. After stirring for 30 min., a solution of tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (50 mg, 0.173 mmol) in THF (1.0 mL) was added to the reaction mixture at the same temperature. After stirring for 5 minutes the reaction mixture was diluted with MeOH (1 mL), sat. aq. NH4Cl (5 mL), brine (5 mL) and EtOAc (10 mL). The layers were separated and the aqueous layer was extracted with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated. The resulting residue was purified by flash column chromatography to provide the title compound. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.07 (s, 1H) 7.68-7.80 (m, 1H) 7.60 (dd, J=8.08, 1.52 Hz, 1H) 7.52 (d, J=3.79 Hz, 1H) 6.91 (s, 1H) 6.72-6.86 (m, 2H) 6.49 (dd, J=4.80, 1.01 Hz, 1H) 6.32 (d, J=5.05 Hz, 1H) 3.85 (s, 3H) 2.53 (s, 3H) 1.51-1.61 (m, 9H).

後処理

  1. stirringAfter stirring for 5 minutes the reaction mixture
  2. customThe layers were separated
  3. extractionthe aqueous layer was extracted with EtOAc
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by flash column chromatography

出典と根拠

ORDレコード
ord-5b075f8a6cc64c7a807d620006bd02d4
出典データセット
uspto-grants-2015_06
特許番号
US09056874B2

反応ノート

読み込み中…