Sodium borohydride → HCID 66606581, compound

HRID 1811007Notes

Reaction equation

HRID 1811007 reaction equation
[Br:1][C:2]1[C:3]([CH3:19])=[C:4]([N:8]2[C:16](=[O:17])[CH:15]3[CH:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)[C:9]2=[O:18])[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+]>CO>[Br:1][C:2]1[C:3]([CH3:19])=[C:4]([N:8]2[CH:16]([OH:17])[CH:15]3[CH:10]([CH2:11][CH2:12][CH2:13][CH2:14]3)[C:9]2=[O:18])[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 66606066HCID 66606066, compound2×

Product 1

HCID 66606581HCID 66606581, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A suspension of 2-(3-bromo-2-methylphenyl)hexahydro-1H-isoindole-1,3(2H)-dione (Intermediate 3-6, 4.5 g, 13.97 mmol) in methanol (150 mL) was treated with sodium borohydride (2.64 g, 69.8 mmol) and stirred at rt for 4 h. The mixture was concentrated, and the residue was dissolved in DCM, washed with NaHCO3 (aq) and water, and dried and concentrated to provide 2-(3-bromo-2-methylphenyl)-3-hydroxyoctahydro-1H-isoindol-1-one as a yellow solid (3.94 g, 87%). Mass spectrum m/z 324, 326 (M+H)+. Without purification, a portion of this material (1.8 g, 5.55 mmol) was dissolved in DCM (50 mL) and treated with triethylsilane (6.46 g, 55.5 mmol). The solution was treated dropwise at rt with TFA (2.14 mL, 27.8 mmol) and stirred at rt for 30 min. The mixture was concentrated and the residue was dissolved in DCM, washed with NaHCO3 (aq) and water. The organic phase was dried and concentrated. The residue was purified by column chromatography (eluting with hexane-EtOAc) to provide 2-(3-bromo-2-methylphenyl)octahydro-1H-isoindol-1-one (Intermediate 4-1, 1.35 g, 79%). 1H NMR (400 MHz, chloroform-d) δ 7.48-7.53 (1 H, m), 7.06-7.09 (2 H, m), 3.78 (1 H, dd, J=9.5, 5.7 Hz), 3.19 (1 H, dd, J=9.5, 2.4 Hz), 2.64-2.70 (1 H, m), 2.45-2.54 (1 H, m), 2.30 (3 H, s), 2.10-2.17 (1 H, m), 1.80-1.88 (1 H, m), 1.62-1.71 (2 H, m), 1.56-1.62 (1 H, m), 1.40-1.51 (1 H, m), 1.31 (2 H, s). Mass spectrum m/z 308, 310 (M+H)+. Also isolated was 2-(3-bromo-2-methylphenyl)-2,3,4,5,6,7-hexahydro-1H-isoindol-1-one (Intermediate 4-2, 224 mg, 13%). 1H NMR (400 MHz, chloroform-d) δ 7.51-7.55 (1 H, m), 7.05-7.14 (2 H, m), 4.09 (2 H, t, J=1.9 Hz), 2.28-2.37 (4 H, m), 2.28 (3 H, s), 1.73-1.85 (4 H, m). Mass spectrum m/z 306, 308 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutionthe residue was dissolved in DCM
  3. washwashed with NaHCO3 (aq) and water
  4. customdried
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-68885ed947844db6bd6d1d467d225c78
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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