Dimethylformamide → 5-[(Phenylmethyl)oxy]-1-(phenylsulfonyl)-1H-indole-2-carbaldehyde

HRID 1188322Notes

Reaction equation

HRID 1188322 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH:13]=[CH:12]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Li]CCCC.CN([CH:35]=[O:36])C.[NH4+].[Cl-]>C1COCC1>[C:1]1([CH2:7][O:8][C:9]2[CH:10]=[C:11]3[C:15](=[CH:16][CH:17]=2)[N:14]([S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[C:13]([CH:35]=[O:36])=[CH:12]3)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 25517Ammonium ChlorideHCID 118246245-(Phenylmethoxy)-1-phenylsulfonylindoleHCID 178418339Butyllithium

Product 1

HCID 578004025-[(Phenylmethyl)oxy]-1-(phenylsulfonyl)-1H-indole-2-carbaldehydeYield 77%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 5-[(phenylmethyl)oxy]-1-(phenylsulfonyl)-1H-indole (1.5 g, 4.12 mmol) in THF (20 mL), under N2, at −78° C., was added n-BuLi (2.5M solution in hexane, 2.15 mL, 5.37 mmol) dropwise. After stirring at −78° C. for 30 min, anhydrous DMF (0.54 g, 7.42 mmol) was added. After 5 min, the −78° C. bath was replaced with an ice bath. After 45 min, sat'd NH4Cl solution (20 mL) was added and the mixture was partitioned between Et2O and water. The organic phase was washed with water and sat'd brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (20-70% CH2Cl2-hexanes gradient) to afford the title compound (1.24 g, 77% yield): 1H NMR (400 MHz, CDCl3) δ 10.5 (s, 1H), 8.14 (d, J=9.3 Hz, 1H), 7.74 (d, J=7.6 Hz, 2H), 7.53 (t, J=7.6 Hz, 1H), 7.43-7.31 (m, 8H), 7.22 (dd, J=9.3, 2.4 Hz, 1H), 7.06 (d, J=2.4 Hz, 1H), 5.06 (s, 2H); MS (ES) m/z 392 (M+1).

Workup

  1. waitAfter 5 min
  2. customthe −78° C. bath was replaced with an ice bath
  3. waitAfter 45 min
  4. additionwas added
  5. customthe mixture was partitioned between Et2O and water
  6. washThe organic phase was washed with water
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by flash chromatography (20-70% CH2Cl2-hexanes gradient)

Sources & evidence

ORD record
ord-414d6e110f1b48ef8789b95ad48ff3f9
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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