Ammonium Chloride → 1-[3-Phenyl-1-(toluene-4-sulfonyl)-1H-indol-2-yl]ethanol

HRID 242875Notes

Reaction equation

HRID 242875 reaction equation
[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[C:8]=2[CH:26]=[O:27])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:28][Mg]Br.[NH4+].[Cl-]>C1COCC1.C(OCC)C>[C:1]1([C:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[N:9]([S:16]([C:19]3[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=3)(=[O:17])=[O:18])[C:8]=2[CH:26]([OH:27])[CH3:28])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 547518363-Phenyl-1-(toluene-4-sulfonyl)-1H-indole-2-carbaldehyde2×HCID 178418573HCID 178418573, compound2×

Product 1

HCID 681570351-[3-Phenyl-1-(toluene-4-sulfonyl)-1H-indol-2-yl]ethanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 3-phenyl-1-(toluene-4-sulfonyl)-1H-indole-2-carbaldehyde (2.11 g, 5.62 mmol) in THF (30 mL) at −78° C. and under a nitrogen atmosphere, was added 3.0M methylmagnesium bromide in diethyl ether (2.6 mL). The mixture was stirred at 0° C. for 30 min then additional 3.0M methylmagnesium bromide in diethyl ether (0.3 mL) added. After 15 min, the reaction mixture was poured into a saturated solution of NH4Cl and extracted with EtOAc (×2). The combined organic fractions were washed with water, dried (Na2SO4) and concentrated in vacuo. The crude material was combined with a second portion of crude reaction mixture obtained following the same method (starting from 140 mg, 3.73 mmol of 3-phenyl-1-(toluene-4-sulfonyl)-1H-indole-2-carbaldehyde) and the combined batches were purified by column chromatography (Si—PCC, gradient 20-100% DCM in pentane) affording the title compound as a gum which solidified on standing (2.02 g, 86%). 1H NMR (CDCl3, 400 MHz): δ 8.07 (1H, d, J=8.35), 7.80-7.75 (2H, m), 7.51-7.38 (5H, m), 7.33-7.26 (2H, m), 7.20-7.14 (3H, m), 5.25-5.15 (1H, m), 4.06 (1H, d, J=11.01 Hz), 2.31 (3H, s), 1.70 (3H, d, J=6.88 Hz)

Workup

  1. waitAfter 15 min
  2. extractionextracted with EtOAc (×2)
  3. washThe combined organic fractions were washed with water
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customreaction mixture
  7. customobtained
  8. customthe combined batches were purified by column chromatography (Si—PCC, gradient 20-100% DCM in pentane)

Sources & evidence

ORD record
ord-2da200b888ed46b1834a2604c57dec56
Source dataset
uspto-grants-2014_02
Patent number
US08653089B2

Reaction notes

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