Triphenylphosphine → HCID 67534128, compound

HRID 1064783Notes

Reaction equation

HRID 1064783 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8]([CH2:10][CH2:11][N:12]3[CH2:16][CH2:15][CH2:14][C@H:13]3[CH3:17])=[CH:7][C:6]=2[CH:18]=1.[C:19]([C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1)#[N:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O.CN1C(=O)CCC1.CS(O)(=O)=O>C(O)(C)C.O>[CH3:17][C@@H:13]1[CH2:14][CH2:15][CH2:16][N:12]1[CH2:11][CH2:10][C:8]1[S:9][C:5]2[CH:4]=[CH:3][C:2]([C:24]3[CH:25]=[CH:26][C:21]([C:19]#[N:20])=[CH:22][CH:23]=3)=[CH:18][C:6]=2[CH:7]=1

Participants

8

Reactant 5

HCID 11776TriphenylphosphineHCID 62657Potassium Phosphate, TribasicHCID 27343264-Cyanophenylboronic acidHCID 67534555HCID 67534555, compoundHCID 131725232HCID 131725232, compound

Product 1

HCID 67534128HCID 67534128, compoundYield 86.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
65 °C

Procedure

The product from Example 165E (0.4 g), 4-cyanophenylboronic acid(0.45 g, 2.5 eq), triphenylphosphine (65 mg, 0.2 eq), and bistriphenylphosphine palladium dichloride (87 mg, 0.1 eq) in isopropanol (8 mL) was treated with potassium phosphate (0.52 g, 2 eq) in 8 mL of water. The mixture was heated at 65° C. under nitrogen for 25 hours, allowed to cool to room temperature, and treated with H2O:NMP:MeSO3H (70:20:10, 10 mL). The mixture was extracted with toluene (2×10 mL) and the acidic aqueous phase was basified to pH 10 using 50% NaOH. The basified solution was extracted with methylene chloride (10 mL), washed with water (2×10 mL), and concentrated to a brown oil. The brown oil was dissolved in EtOAc (20 mL), washed with water (2×10 mL), and concentrated. The residue was purified by column chromatography (silica gel, 10:90 MeOH:CHCl3) to provide the title compound (0.37 g). MS m/z 347(M+H)+. The free base was dissolved in 5 mL of MeOH and added to L-tartaric acid (0.16 g, 1 eq) in 5 mL of MeOH. The mixture was concentrated to dryness, and crystallized from EtOAc/EtOH to give the tartrate salt (0.33 g). 1H NMR(DMSO-d6) δ 1.17 (doublet), 1.41-1.49(multiplet), 1.74-1.82(multiplet), 1.97-2.03(multiplet), 2.55-2.59(multiplet), 2.80 (multiplet), 3.12-3.37(multiplet), 4.11(singlet), 7.33 (singlet), 7.66 (doublet), 7.93(singlet), 8.02(doublet), 8.13(doublet).

Workup

  1. temperatureto cool to room temperature
  2. extractionThe mixture was extracted with toluene (2×10 mL)
  3. extractionThe basified solution was extracted with methylene chloride (10 mL)
  4. washwashed with water (2×10 mL)
  5. concentrationconcentrated to a brown oil
  6. dissolutionThe brown oil was dissolved in EtOAc (20 mL)
  7. washwashed with water (2×10 mL)
  8. concentrationconcentrated
  9. customThe residue was purified by column chromatography (silica gel, 10:90 MeOH:CHCl3)

Sources & evidence

ORD record
ord-d99d05f289984cb3904a437f70cc4139
Source dataset
uspto-grants-2005_11
Patent number
US06969730B2

Reaction notes

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