Chlorosuccinimide → 6-(5-(Tributylstannyl)isoxazol-3-yl)isoquinoline

HRID 598847Notes

Reaction equation

HRID 598847 reaction equation
[CH:1]1[C:10]2[C:5](=[CH:6][C:7](/[CH:11]=[N:12]/[OH:13])=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.ClN1C(=O)CCC1=O.[CH2:22]([Sn:26]([CH2:33][CH2:34][CH2:35][CH3:36])([CH2:29][CH2:30][CH2:31][CH3:32])[C:27]#[CH:28])[CH2:23][CH2:24][CH3:25]>CN(C=O)C>[CH2:33]([Sn:26]([CH2:29][CH2:30][CH2:31][CH3:32])([CH2:22][CH2:23][CH2:24][CH3:25])[C:27]1[O:13][N:12]=[C:11]([C:7]2[CH:6]=[C:5]3[C:10](=[CH:9][CH:8]=2)[CH:1]=[N:2][CH:3]=[CH:4]3)[CH:28]=1)[CH2:34][CH2:35][CH3:36]

Participants

5

Reactant 3

HCID 31398ChlorosuccinimideHCID 621176EthynyltributyltinHCID 136166442(NE)-N-(isoquinolin-6-ylmethylidene)hydroxylamine

Product 1

HCID 579505796-(5-(Tributylstannyl)isoxazol-3-yl)isoquinolineYield 31.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
5 °C

Procedure

To a solution of (E)-isoquinoline-6-carbaldehyde oxime (2.14 g, 12.4 mmol) in 60 mL of DMF at 0° C. was added 1-chloropyrrolidine-2,5-dione (1.66 g, 12.4 mmol) (commercially available from Aldrich). The mixture was stirred for 10 minutes and then heated to 5° C. After 2½ hours, the DMF was removed by rotary evaporation. The residue was dissolved in 100 mL of THF and chilled to 0° C. To this mixture was added tributyl(ethynyl)stannane (4.50 g, 14.3 mmol) (commercially available from Aldrich). TEA (3.81 mL, 27.3 mmol) was then added dropwise. The mixture was gradually warmed to room temperature over 12 hours. The reaction was quenched with 50 mL of aqueous NH4Cl and diluted with 50 mL of water. The mixture was partitioned in a separatory funnel. The aqueous portion was extracted twice with 100 mL of EtOAc, and the combined organic layers were washed with 100 mL of brine and dried over MgSO4. Filtration and concentration under reduced pressure, followed by flash chromatography on silica gel (5% to 30% EtOAc/hexanes), afforded 6-(5-(tributylstannyl)isoxazol-3-yl)isoquinoline (1.87 g, 31.0% yield) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 9.29 (s, 1H), 8.58 (d, J=5.8 Hz, 1H), 8.26 (s, 1H), 8.14 (dd, J=1.3 Hz, 8.5 Hz, 1H), 8.05 (d, J=8.5 Hz, 1H), 7.72 (d, J=5.7 Hz, 1H), 6.83 (s, 1H), 1.65-1.57 (m, 6H), 1.38 (q, 7.3 Hz, 6H), 1.23 (t, J=8.2 Hz, 6H), 0.92 (t, 7.2 Hz, 9H).

Workup

  1. waitAfter 2½ hours
  2. customthe DMF was removed by rotary evaporation
  3. dissolutionThe residue was dissolved in 100 mL of THF
  4. temperaturechilled to 0° C
  5. temperatureThe mixture was gradually warmed to room temperature over 12 hours
  6. customThe reaction was quenched with 50 mL of aqueous NH4Cl
  7. additiondiluted with 50 mL of water
  8. customThe mixture was partitioned in a separatory funnel
  9. extractionThe aqueous portion was extracted twice with 100 mL of EtOAc
  10. washthe combined organic layers were washed with 100 mL of brine
  11. dry with materialdried over MgSO4
  12. filtrationFiltration and concentration under reduced pressure

Sources & evidence

ORD record
ord-908f456eb20d44d39f2846fe92a42f55
Source dataset
uspto-grants-2011_03
Patent number
US07897619B2

Reaction notes

Loading…