Tris(1,1-dimethylethyl)phosphine → HCID 59004667, compound

HRID 1668473Notes

Reaction equation

HRID 1668473 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH:11]1[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]1)[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+]>[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.O1CCCC1>[CH3:17][N:14]1[CH2:15][CH2:16][CH:11]([N:7]2[C:8]3[C:4](=[CH:3][C:2]([NH2:35])=[CH:10][CH:9]=3)[CH:5]=[CH:6]2)[CH2:12][CH2:13]1

Participants

6

Reactant 3

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2733832Lithium HexamethyldisilazideHCID 59004638HCID 59004638, compound

Product 1

HCID 59004667HCID 59004667, compoundYield 49.2%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

Compound 80 (265 mg, 0.904 mmol), Tris(dibenzylideneacetone) dipalladium (0) (82.7 mg, 0.0904 mmol) and anhydrous tetrahydrofuran (20 mL) were charged to a dry argon purged flask fitted with magnetic stir bar and condenser. A solution of tri-tert-butylphosphine (10 wt % in hexane, 365.7 mg, 538 ul, 0.1808 mmol) is added followed by dropwise addition of a 1 M tetrahydrofuran solution of lithium bis(trimethylsilyl)amide (2.71 ml, 2.710 mmol) and mixture refluxed for a period of 45 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 (EtOAc:methanol:Et3N, 8:1:1) to yield a pale yellow solid 81 (102 mg, 49.2%). 1H NMR (DMSO-d6) δ: 1.80-1.98 (m, 4H), 2.11 (dt, 2H, J=11.2, 3.5 Hz), 2.23 (s, 3H), 2.88 (d, 2H, J=11.6 Hz), 4.08-4.19 (m, 1H), 4.46 (brs, 2H), 6.13 (d, 1H, J=3.0 Hz), 6.51 (dd, 1H, J=8.8, 2.1 Hz), 6.67 (d, 1H, J=2.0 Hz), 7.18 (d, 1H, J=8.6 Hz), 7.24 (d, 1H, J=3.1 Hz); EI-MS (m/z, %): 229 (M+, 100%).

Workup

  1. customfitted with magnetic stir bar and condenser
  2. temperaturerefluxed for a period of 45 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 (EtOAc:methanol:Et3N, 8:1:1)

Sources & evidence

ORD record
ord-9991ba76d4334eb6b954406ee9a17779
Source dataset
uspto-grants-2011_08
Patent number
US07989447B2

Reaction notes

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