HCID 58986346, compound → HCID 66658608, compound

HRID 420805Notes

Reaction equation

HRID 420805 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)=[CH:14][CH:15]=2)[C:10]([CH:24]=[O:25])=[C:9]1[CH:26]([CH3:28])[CH3:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][Mg+].[Br-]>C1COCC1>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH:18]3[CH2:23][CH2:22][CH2:21][CH2:20][O:19]3)=[CH:14][CH:15]=2)[C:10]([CH:24]([OH:25])[CH3:29])=[C:9]1[CH:26]([CH3:28])[CH3:27])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 58986346HCID 58986346, compound2×HCID 178418689HCID 178418689, compound

Product 1

HCID 66658608HCID 66658608, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

General Procedure C. To a −78° C. solution of (1-benzyl-2-isopropyl-5-(tetrahydropyran-2-yloxy)-1H-indole-3-carboxaldehyde (Compound 13, 200 mg, 0.55 mmol) in THF (5 mL) was added MeMgBr (3 M solution in THF, 1 mL, 3 mmol). The solution was stirred between −78° C. and −10° C. for 4 h, and then the reaction was quenched at −78° C. by adding EtOAc (2 mL) and water (5 mL). The mixture was warmed to room temperature and diluted with EtOAc (50 mL). The reaction was quickly washed with ice cold aqueous NH4Cl (5 mL), and brine (10 mL), and dried (Na2SO4), and the solvent was removed under vacuum to give 1-(1-benzyl-2-isopropyl-5-(tetrahydropyran-2-yloxy)-1H-indol-3-yl)ethanol as a mixture of two diastereomers that were used directly in the next step without further purification or characterization. Thus, crude 1-(1-benzyl-2-isopropyl-5-(tetrahydropyran-2-yloxy)-1H-indol-3-yl)ethanol (200 mg, 0.51 mmol) was oxidized to 1-(1-benzyl-2-isopropyl-5-(tetrahydropyran-2-yloxy)-1H-indol-3-yl)ethanone (Compound 14) by General Procedure B.

Workup

  1. customthe reaction was quenched at −78° C.
  2. additionby adding EtOAc (2 mL) and water (5 mL)
  3. additiondiluted with EtOAc (50 mL)
  4. washThe reaction was quickly washed with ice cold aqueous NH4Cl (5 mL), and brine (10 mL)
  5. dry with materialdried (Na2SO4)
  6. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-87733ba2e6864f99baff707548548e0b
Source dataset
uspto-grants-2012_01
Patent number
US08097644B2

Reaction notes

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