Triphenylphosphine → HCID 44194027, compound

HRID 1402722Notes

Reaction equation

HRID 1402722 reaction equation
C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cl:20][C:21]1[N:22]=[N:23][C:24](Cl)=[CH:25][CH:26]=1.[CH3:28][C@@H:29]1[CH2:33][CH2:32][CH2:31][N:30]1[CH2:34][CH2:35][CH2:36][O:37][C:38]1[CH:43]=[CH:42][C:41](B2OC(C)(C)C(C)(C)O2)=[CH:40][CH:39]=1.C([O-])(O)=O.[Na+]>C1COCC1.CCO.CC([O-])=O.CC([O-])=O.[Pd+2]>[Cl:20][C:21]1[N:22]=[N:23][C:24]([C:41]2[CH:42]=[CH:43][C:38]([O:37][CH2:36][CH2:35][CH2:34][N:30]3[CH2:31][CH2:32][CH2:33][C@H:29]3[CH3:28])=[CH:39][CH:40]=2)=[CH:25][CH:26]=1

Participants

8

Reactant 4

HCID 11776TriphenylphosphineHCID 673313,6-DichloropyridazineHCID 516892Sodium BicarbonateHCID 53363441HCID 53363441, compound

Product 1

HCID 44194027HCID 44194027, compoundYield 90.4%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
80 °C

Procedure

Pd(OAc)2 trimer (2.02 g, 9.0 mmol) and Ph3P (9.36 g, 35.6 mmol) were suspended in anhydrous THF (300 mL) and stirred vigorously under a nitrogen atmosphere for 10 min. 3,6-dichloropyridazine (26.82 g, 180 mmol) was added as a solid and stirring was continued for 10 min. (R)-2-Methyl-1-{3-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenoxy]-propyl}-pyrrolidine (11.76 g, 34 mmol) was dissolved in a mixture of THF (200 mL) and EtOH (100 mL) and added dropwise to the reaction mixture. Saturated NaHCO3 solution (360 mL) was introduced. The reaction mixture was heated at 80° C. for 15 h, cooled and was evaporated to a residue, which was taken up in CH2Cl2 (300 mL) and washed with water and saturated NaHCO3 solution. The CH2Cl2phase was dried (Na2SO4) and evaporated. The product was obtained by ISCO chromatography on silica gel, eluting with EtOAc initially, then with a mixture of EtOAc/CH3OH (9:1) to provide the title compound (10.20 g, 90%) as a cream solid, m.p. 107-108.5° C.; 1H NMR (CDCl3) 1.10 (d, 3H, —CH3), 2.99 (m, 2H, —CH2—), 3.18 (m, 2H, —CH2—), 4.10 (m, 2H, —CH2—), 7.04 (d, 2H, Ar—H), 7.50 (d, 1H, C—H), 7.78 (d, 1H, C—H), 7.99 (d, 2H, Ar—H) (representative signals only); HPLC retention time 6.893 min. (elution solvents CH3CN w/0.1% TFA and H2O w/0.1% TFA; column: Agilent Zorbax RX-C8 4.6 mm×150 mm w/5 μm particle size; method: 10-100% CH3CN over 20 min., 100% CH3CN for an additional 4.5 minutes; flow rate: 1.6 mL/min; System: Agilent 1100 HPLC).

Workup

  1. stirringstirring
  2. waitwas continued for 10 min.
  3. additionadded dropwise to the reaction mixture
  4. temperaturecooled
  5. customwas evaporated to a residue, which
  6. washwashed with water and saturated NaHCO3 solution
  7. dry with materialThe CH2Cl2phase was dried (Na2SO4)
  8. customevaporated
  9. customThe product was obtained by ISCO chromatography on silica gel
  10. washeluting with EtOAc initially
  11. additionwith a mixture of EtOAc/CH3OH (9:1)

Sources & evidence

ORD record
ord-6b74cfc7f7f5409e8108344c359a2da7
Source dataset
uspto-grants-2014_12
Patent number
US08912183B2

Reaction notes

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