2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → HCID 54591522, compound

HRID 1260200Notes

Reaction equation

HRID 1260200 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:28]=[CH:29][CH:30]=1)[CH2:5][N:6]1[C:10]([CH3:11])=[CH:9][C:8]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([S:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)=[N:7]1.[Si]([O:48][CH:49]1[CH2:54][CH2:53][NH:52][CH2:51][CH2:50]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.CC(C)([O-])C.[Na+]>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH3:11][C:10]1[N:6]([CH2:5][C:4]2[CH:3]=[C:2]([N:52]3[CH2:53][CH2:54][CH:49]([OH:48])[CH2:50][CH2:51]3)[CH:30]=[CH:29][CH:28]=2)[N:7]=[C:8]([C:12]2[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([S:23][C:24]([F:27])([F:26])[F:25])=[CH:19][CH:18]=3)[N:13]=2)[CH:9]=1

Participants

8

Reactant 4

HCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 58072141HCID 58072141, compoundHCID 58072151HCID 58072151, compound

Product 1

HCID 54591522HCID 54591522, compound

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 500 mg (1.01 mmol) of the compound from Example 10A, 514 mg (1.51 mmol) of the compound from Example 9A, 92 mg (0.101 mmol) of tris(dibenzylideneacetone)dipalladium(0), 96 mg (0.202 mmol) of 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl (X-Phos) and 194 mg (2.02 mmol) of sodium tert-butoxide in 10 ml of toluene was heated to 80° C. under argon in a microwave oven (Biotage Initiator, dynamic control of the incident power) for 3 h. After cooling to RT, 100 ml of water were added to the reaction mixture, which was extracted three times with approx. 100 ml each time of ethyl acetate. The combined organic extracts were washed successively with water and saturated sodium chloride solution, dried over anhydrous magnesium sulphate, filtered and finally freed of the solvent on a rotary evaporator. The resulting crude product, which was the corresponding silyl-protected intermediate, was purified by means of MPLC (approx. 70 g of silica gel, eluent: cyclohexane→5:1 cyclohexane/ethyl acetate). Subsequently, this product was dissolved in 3.5 ml of THF, and 3.5 ml (3.5 mmol) of a 1 M solution of tetra-n-butylammonium fluoride (TBAF) in THF were added. After this mixture had been stirred at RT for 20 min, it was concentrated on a rotary evaporator. The title compound was isolated by means of MPLC (approx. 20 g of silica gel, eluent: 2:1→1:3 cyclohexane/ethyl acetate). After concentration and drying, the product was once again stirred with pentane/diethyl ether. 65 mg (12% of theory) of the title compound were thus obtained.

Workup

  1. temperatureAfter cooling to RT
  2. extractionwas extracted three times with approx. 100 ml each time of ethyl acetate
  3. washThe combined organic extracts were washed successively with water and saturated sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulphate
  5. filtrationfiltered
  6. customfinally freed of the solvent on a rotary evaporator
  7. customwas purified by means of MPLC (approx. 70 g of silica gel, eluent: cyclohexane→5:1 cyclohexane/ethyl acetate)
  8. dissolutionSubsequently, this product was dissolved in 3.5 ml of THF
  9. addition3.5 ml (3.5 mmol) of a 1 M solution of tetra-n-butylammonium fluoride (TBAF) in THF were added
  10. concentrationit was concentrated on a rotary evaporator

Sources & evidence

ORD record
ord-f686f930abd44a658f5d26443527c643
Source dataset
uspto-grants-2013_06
Patent number
US08470811B2

Reaction notes

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