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

HRID 2174090Notes

Reaction equation

HRID 2174090 reaction equation
[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]

Participants

9

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolventHCID 25517Ammonium ChlorideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-5b075f8a6cc64c7a807d620006bd02d4
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

Loading…