Trifluoroacetic acid → HCID 59375026, compound

HRID 1811008Notes

Reaction equation

HRID 1811008 reaction equation
[Br:1][C:2]1[C:3]([CH3:23])=[C:4]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[C:13]([C:18]([CH3:21])([CH3:20])[CH3:19])[CH:14]=3)[C:9]2=O)[CH:5]=[CH:6][CH:7]=1.[BH4-].[Na+].C(O)(C(F)(F)F)=O.C([SiH](CC)CC)C>CO.C(Cl)Cl>[Br:1][C:2]1[C:3]([CH3:23])=[C:4]([N:8]2[CH2:9][C:10]3[C:15](=[CH:14][C:13]([C:18]([CH3:19])([CH3:20])[CH3:21])=[CH:12][CH:11]=3)[C:16]2=[O:17])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 12052TriethylsilaneHCID 4311764Sodium borohydride2×HCID 66606043HCID 66606043, compound2×

Product 1

HCID 59375026HCID 59375026, compoundYield 28%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

A suspension of 2-(3-bromo-2-methylphenyl)-5-tert-butylisoindoline-1,3-dione (Intermediate 3-2, 1.0 g, 2.69 mmol) in methanol (20 mL) was treated with sodium borohydride (203 mg, 5.37 mmol) and stirred at rt. After a few minutes, additional sodium borohydride (203 mg, 5.37 mmol) was added. After 40 min, the mixture was concentrated, and the residue was dissolved in DCM, washed with water and brine, and dried and concentrated to provide a white solid. This material was dissolved in DCM (10 mL) and treated with TFA (10 mL) and stirred for a few minutes at rt, then was treated with triethylsilane (6.40 mL, 40.1 mmol) and stirred at rt for 2.5 h. 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)-6-tert-butylisoindolin-1-one (Intermediate 4-3, 134 mg, 28%). 1H NMR (400 MHz, chloroform-d) δ 7.99 (1 H, d, J=1.32 Hz), 7.68 (1 H, dd, J=7.91, 1.76 Hz), 7.60 (1 H, dd, J=7.69, 1.10 Hz), 7.45 (1 H, d, J=7.91 Hz), 7.19-7.23 (1 H, m), 7.15 (1 H, t, J=7.69 Hz), 4.68 (2 H, s), 2.31 (3 H, s), 1.39 (9 H, s). Mass spectrum m/z 358, 360 (M+H)+. Also isolated was 2-(3-bromo-2-methylphenyl)-5-tert-butylisoindolin-1-one (Intermediate 4-4, 250 mg, 52%). 1H NMR (400 MHz, chloroform-d) δ 7.88 (1 H, d, J=7.91 Hz), 7.59 (2 H, dd, J=8.13, 2.86 Hz), 7.53 (1 H, s), 7.20-7.23 (1 H, m), 7.12-7.17 (1 H, m), 4.69 (2 H, s), 2.31 (3 H, s), 1.40 (9 H, s). Mass spectrum m/z 358, 260 (M+H)+.

Workup

  1. waitAfter a few minutes
  2. concentrationthe mixture was concentrated
  3. dissolutionthe residue was dissolved in DCM
  4. washwashed with water and brine
  5. customdried
  6. concentrationconcentrated
  7. customto provide a white solid
  8. stirringstirred for a few minutes at rt
  9. stirringstirred at rt for 2.5 h
  10. concentrationThe mixture was concentrated
  11. dissolutionthe residue was dissolved in DCM
  12. washwashed with NaHCO3 (aq) and water
  13. customThe organic phase was dried
  14. concentrationconcentrated
  15. customThe residue was purified by column chromatography (eluting with hexane-EtOAc)

Sources & evidence

ORD record
ord-a48e459440b94c659b717c12b929414a
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

Loading…