Lithium Chloride → tert-Butyl-4-((5-cyanobenzo[d]oxazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

HRID 2174075Notes

Reaction equation

HRID 2174075 reaction equation
[O:1]1[C:5]2[CH:6]=[CH:7][C:8]([C:10]#[N:11])=[CH:9][C:4]=2[N:3]=[CH:2]1.[Li+].[Cl-].[CH:14]([C:16]1[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]2[C:17]=1[CH:18]=[CH:19][N:20]2[C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])=[O:15]>C1COCC1.[NH4+].[Cl-].[Cl-].[Na+].O>[C:10]([C:8]1[CH:7]=[CH:6][C:5]2[O:1][C:2]([CH:14]([OH:15])[C:16]3[C:24]([O:25][CH3:26])=[CH:23][C:22]([CH3:27])=[C:21]4[C:17]=3[CH:18]=[CH:19][N:20]4[C:28]([O:30][C:31]([CH3:33])([CH3:32])[CH3:34])=[O:29])=[N:3][C:4]=2[CH:9]=1)#[N:11]

Participants

7

Reactant 3

HCID 433294Lithium ChlorideHCID 203806861,3-Benzoxazole-5-carbonitrileHCID 72191522tert-Butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate

Product 1

HCID 86701709tert-Butyl-4-((5-cyanobenzo[d]oxazol-2-yl)(hydroxy)methyl)-5-methoxy-7-methyl-1H-indole-1-carboxylate

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 25517Ammonium ChlorideSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

To a solution of benzo[d]oxazole-5-carbonitrile (CAS #:132227-01-1) (0.996 g, 6.91 mmol) in THF (20 mL), TMPMgCl.LiCl (1 M in THF) (6.91 mL, 6.91 mmol) was added at −78° C. After stirring for 30 min, tert-butyl 4-formyl-5-methoxy-7-methyl-1H-indole-1-carboxylate (Example 19-D) (1.00 g, 3.46 mmol) was added at −78° C. Then, the reaction mixture was warmed to rt. After stirring for 10 min, the reaction was heated at 50° C. After stirring for 1.5 h, the reaction mixture was cooled to rt, and diluted with aq. NH4Cl and brine. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with a 1:1 solution of 1M aq. NaHSO4 and brine, dried over Na2SO4, filtered, and concentrated. The residue was purified by flash column chromatography on silica gel (heptane/EtOAc=100:0 to 40:60) to give the title compound. MS (ESI) m/z 432.3 (MH).

Workup

  1. stirringAfter stirring for 10 min
  2. temperaturethe reaction was heated at 50° C
  3. stirringAfter stirring for 1.5 h
  4. temperaturethe reaction mixture was cooled to rt
  5. customThe layers were separated
  6. extractionthe aqueous layer was extracted with EtOAc
  7. washThe combined organic layers were washed with a 1:1 solution of 1M aq. NaHSO4 and brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash column chromatography on silica gel (heptane/EtOAc=100:0 to 40:60)

Sources & evidence

ORD record
ord-b68b35316b9846bf89cc9d3b6033f441
Source dataset
uspto-grants-2015_06
Patent number
US09056874B2

Reaction notes

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