Triphenylphosphine → HCID 66933521, compound

HRID 1364173Notes

Reaction equation

HRID 1364173 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([Cl:11])[CH:10]=1)[C:7](=[O:12])[N:6]([C@H:13]([CH:15]1[CH2:17][CH2:16]1)[CH3:14])[CH2:5]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:37]([Si:39]([CH3:42])([CH3:41])[CH3:40])#[CH:38].[SiH4]>C(NC(C)C)(C)C.C([O-])(=O)C.[Cu+2].C([O-])(=O)C.C1C=CC(C#N)=CC=1.C1C=CC(C#N)=CC=1.Cl[Pd]Cl>[Cl:11][C:9]1[CH:10]=[C:2]([C:38]#[C:37][Si:39]([CH3:42])([CH3:41])[CH3:40])[CH:3]=[C:4]2[C:8]=1[C:7](=[O:12])[N:6]([C@H:13]([CH:15]1[CH2:17][CH2:16]1)[CH3:14])[CH2:5]2

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 23953SilaneHCID 66111TrimethylsilylacetyleneHCID 66933275HCID 66933275, compound

Product 1

HCID 66933521HCID 66933521, compoundYield 93%

Reagents, catalysts & solvents 3

HCID 8895Cupric acetateCatalystHCID 498840Bis(benzonitrile)palladium chlorideCatalystHCID 7912DiisopropylamineSolvent

Procedure

5-bromo-7-chloro-2-((S)-1-cyclopropylethyl)isoindolin-1-one (5.0 g, 15.89 mmol) was placed in a 3-neck flask, fitted with an internal thermocouple and dissolved in 150 mL of degassed diisopropyl amine. To this solution was added copper (II) acetate (0.14 g, 0.79 mmol), triphenylphosphine (0.417 g, 1.59 mmol) and bis(benzonitrile)dichloropalladium (II) (0.30 g, 0.79 mmol). Finally, ethynyltrimethylsilane (4.84 mL, 34.96 mmol) was added dropwise over a 20-min period. After the addition of the silane was complete, the reaction mixture was heated to and held at 65° C. until starting material was consumed (as monitored by LC/MS). The reaction was allowed to cool to room temperature and the volatiles were removed under reduced pressure. The material was then filtered through a glass frit and the remaining solids in the frit were rinsed with diethyl ether. The volatiles were again removed under reduced pressure and the concentrated residue was purified by flash chromatography on silica gel eluting with 0 to 40% ethyl acetate in hexane. This afforded the title compound as a tan solid (4.90 g, 93%). 1H NMR (300 MHz, CDCl3) δ ppm 0.18-0.22 (m, 9H) 0.29-0.43 (m, 3H) 0.53-0.62 (m, 1H) 0.88-1.01 (m, 1H) 1.27 (d, 3H) 3.69 (dq, 1H) 4.33 (q, 2H) 7.35 (d, 1H) 7.42 (s, 1H). MS ESI, m/z=332 (M+H). HPLC Method A: 1.05 min.

Workup

  1. customfitted with an internal thermocouple
  2. temperaturethe reaction mixture was heated to and
  3. customheld at 65° C.
  4. customwas consumed (as monitored by LC/MS)
  5. customthe volatiles were removed under reduced pressure
  6. filtrationThe material was then filtered through a glass frit
  7. washthe remaining solids in the frit were rinsed with diethyl ether
  8. customThe volatiles were again removed under reduced pressure
  9. customthe concentrated residue was purified by flash chromatography on silica gel eluting with 0 to 40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-a159c30488eb44f5981c99592d68b692
Source dataset
uspto-grants-2011_02
Patent number
US07888353B2

Reaction notes

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