Tris(furan-2-yl)phosphane → HCID 24802856, compound

HRID 1690720Notes

Reaction equation

HRID 1690720 reaction equation
I[C:2]1[N:6]([CH:7]2[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10](=[O:17])[O:9][C:8]2([CH3:19])[CH3:18])[CH:5]=[N:4][CH:3]=1.O1C=CC=C1P(C1O[CH:33]=[CH:34][CH:35]=1)C1OC=CC=1.C([Sn](CCCC)(CCCC)C1CC1)CCC>CN1CCCC1=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH:34]1([C:2]2[N:6]([CH:7]3[C:16]4[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=4)[C:10](=[O:17])[O:9][C:8]3([CH3:19])[CH3:18])[CH:5]=[N:4][CH:3]=2)[CH2:35][CH2:33]1

Participants

6

Reactant 3

HCID 521585Tris(furan-2-yl)phosphaneHCID 10947505CyclopropyltributylstannaneHCID 57781136HCID 57781136, compound

Product 1

HCID 24802856HCID 24802856, compound

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
95 °C

Procedure

To a flask charged with 4-(5-iodo-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one (350 mg, 0.95 mmol) (Example 2b), tris(dibenzylideneacetone)dipalladium(0) (98 mg, 0.095 mmol) and trifuran-2-yl-phosphane (33 mg, 0.142 mmol) and flushed with N2 is added tributylcyclopropyltin (1.89 g, 5.7 mmol) in degassed N-methylpyrrolidinone (3 mL). The mixture is degassed for 15 min and heated to 95° C. for 25 h. The reaction mixture is quenched with water and extracted with ethyl acetate three times. The organic phase is combined, dried over sodium sulfate, concentrated and the residue is purified by semi-preparative reverse phase HPLC to give 4-(5-cyclopropyl-imidazol-1-yl)-3,3-dimethyl-isochroman-1-one as white solid; (ESI) m/z 283.2 (M+H); 1H NMR (400 MHz, MeOD) δ ppm 0.69 (s, 1 H), 0.81 (br. s, 1 H), 1.09 (br. s, 2 H), 1.29 (s, 3 H), 1.56 (s, 3 H), 1.94 (br. s, 1 H), 5.78 (s, 1 H), 6.68 (s, 1 H), 7.14 (br. s, 1 H), 7.42 (d, J=7.1 Hz, 1 H), 7.63 (td, J=7.6, 1.3 Hz, 1 H), 7.75 (td, J=7.6, 1.3 Hz, 1 H), 8.21 (dd, J=7.8, 1.3 Hz, 1 H).

Workup

  1. customflushed with N2
  2. customThe mixture is degassed for 15 min
  3. customThe reaction mixture is quenched with water
  4. extractionextracted with ethyl acetate three times
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customthe residue is purified by semi-preparative reverse phase HPLC

Sources & evidence

ORD record
ord-b0c1df385c7d4390a9f8f0db418fb067
Source dataset
uspto-grants-2012_04
Patent number
US08153674B2

Reaction notes

Loading…