HCID 2274430, compound → HCID 66730358, compound

HRID 1466306Notes

Reaction equation

HRID 1466306 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[C:7](=O)[N:6]([CH2:12][CH3:13])[C:5]2=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][N:6]([CH2:12][CH3:13])[CH2:5]2

Participants

4

Reactant 2

HCID 2274430HCID 2274430, compoundHCID 21226445Aluminium lithium hydride

Product 1

HCID 66730358HCID 66730358, compoundYield 10.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-bromo-2-ethylisoindoline-1,3-dione (1.27 g, 5 mmol) in THF (10 mL) was added LAH (1 M in THF, 12.5 mL, 12.5 mmol) dropwise over 10 min. The reaction was exothermic. After addition, the resulting mixture was stirred for 30 min at rt. LC-MS showed over reduction. The reaction was quenched with sat. NH4Cl, basified with sat. NaHCO3 and the product was extracted with EtOAc. The mixture was purified by flash chromatography (gradient: MeOH/DCM 0 to 15%) to give the crude 5-bromo-2-ethylisoindoline as a light yellow oil (120 mg). The crude material was converted to the title compound (73 mg, impure, 5% over 2 steps) as a light brown oil using the method for the preparation of Example A51A. 1H NMR (400 MHz, CDCl3) δ 7.37 (d, J=18.4 Hz, 1H), 7.31 (s, 1H, partially overlapping with the peak at 7.30 ppm), 7.30 (d, J=8.0 Hz, 1H, partially overlapping with the peak at 7.31 ppm), 7.13 (d, J=7.6 Hz, 1H), 6.10 (d, J=18.4 Hz, 1H), 3.88 (s, 4H), 1.29 (s, 12H).

Workup

  1. additionAfter addition
  2. customThe reaction was quenched with sat. NH4Cl
  3. extractionthe product was extracted with EtOAc
  4. customThe mixture was purified by flash chromatography (gradient: MeOH/DCM 0 to 15%)

Sources & evidence

ORD record
ord-666b160f983645918df60293d22f91e8
Source dataset
uspto-grants-2015_04
Patent number
US08999968B2

Reaction notes

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