Tris(1,1-dimethylethyl)phosphine → HCID 59004643, compound

HRID 1668489Notes

Reaction equation

HRID 1668489 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:11][C@@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17])[CH:6]=[CH:5]2.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C[Si]([N-:35][Si](C)(C)C)(C)C.[Li+]>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].O1CCCC1>[CH3:17][N:13]1[CH2:14][CH2:15][CH2:16][C@H:12]1[CH2:11][N:7]1[C:8]2[C:4](=[CH:3][C:2]([NH2:35])=[CH:10][CH:9]=2)[CH:5]=[CH:6]1

Participants

6

Reactant 3

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 59004637HCID 59004637, compound

Product 1

HCID 59004643HCID 59004643, compoundYield 80.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

compound 102 (106 mg, 0.362 mmol), tris(dibenzylideneacetone)dipalladium (0) (33.1 mg, 0.0362 mmol) and anhydrous tetrahydrofuran (10 mL) were charged to a dry argon purged flask fitted with magnetic stir bar and condenser. A solution of tri-tert-butylphosphine (146.3 mg, 222 ul, 0.0723 mmol, 10 wt % in hexane) is added followed by dropwise addition of a 1M tetrahydrofuran solution of lithium bis(trimethylsilyl)amide (1.084 ml, 1.084 mmol) and mixture refluxed for a period of 90 minutes. The mixture was cooled to room temperature then to 0° C., quenched with 1M HCl (10 mL) and stirred for 10 minutes. The solution was diluted with ethyl acetate and 5M NH4OH added to adjust pH to 9. The mixture was transferred to a separatory funnel and the organic layer collected. The aqueous layer was further extracted with ethyl acetate and the combined organic layers were washed with brine, dried over magnesium sulphate, filtered, concentrated and the residue purified via chromatography on silica gel (MeOH:CH2Cl2, 1:9) to yield compound 103 (67 mg, 80.8%)as a pale yellow solid. 1H NMR (DMSO-d6) δ 1.40-1.70 (2×m, 4H), 2.08-2.20 (m, 1H), 2.18 (s, 3H), 2.89-2.99 (m, 1H), 3.89 (dd, 1H, J=14.1, 6.9 Hz), 4.12 (dd, 1H, J=14.2, 5.1 Hz), 4.46 (brs, 2H), 6.10 (d, 1H, J=3.0 Hz), 6.51 (dd, 1H, J=8.7, 2.0 Hz), 6.66 (d, 1H, J=2.0 Hz), 7.12-7.15 (m, 2H); ESI-MS (m/z, %): 230 (MH+, 100%).

Workup

  1. customfitted with magnetic stir bar and condenser
  2. temperaturerefluxed for a period of 90 minutes
  3. customto 0° C., quenched with 1M HCl (10 mL)
  4. additionThe solution was diluted with ethyl acetate and 5M NH4OH
  5. additionadded
  6. customThe mixture was transferred to a separatory funnel
  7. customthe organic layer collected
  8. extractionThe aqueous layer was further extracted with ethyl acetate
  9. washthe combined organic layers were washed with brine
  10. dry with materialdried over magnesium sulphate
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customthe residue purified via chromatography on silica gel (MeOH:CH2Cl2, 1:9)

Sources & evidence

ORD record
ord-fd8f90e7640d4885b1e2c6d4b61bb1fc
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

Loading…