Tetramethyltin → HCID 68668567, compound

HRID 216402Notes

Reaction equation

HRID 216402 reaction equation
Br[C:2]1[NH:6][C:5]([CH2:7][C:8]([C:13]2[CH:18]=[CH:17][C:16]([N:19]3[CH:23]=[CH:22][CH:21]=[N:20]3)=[CH:15][CH:14]=2)([OH:12])[CH:9]([F:11])[F:10])=[N:4][C:3]=1[CH2:24][C:25]1([C:28]([F:31])([F:30])[F:29])[CH2:27][CH2:26]1.[CH3:32][Sn](C)(C)C.[Cl-].[Li+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[F-].[K+]>CN(C)C=O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.O.C(OCC)C>[F:10][CH:9]([F:11])[C:8]([C:13]1[CH:18]=[CH:17][C:16]([N:19]2[CH:23]=[CH:22][CH:21]=[N:20]2)=[CH:15][CH:14]=1)([OH:12])[CH2:7][C:5]1[NH:6][C:2]([CH3:32])=[C:3]([CH2:24][C:25]2([C:28]([F:31])([F:30])[F:29])[CH2:27][CH2:26]2)[N:4]=1

Participants

10

Reactant 5

HCID 11661TetramethyltinHCID 11776TriphenylphosphineHCID 433294Lithium ChlorideHCID 522689Potassium FluorideHCID 178520386HCID 178520386, compound

Product 1

HCID 68668567HCID 68668567, compound

Reagents, catalysts & solvents 4

HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

Bis(triphenylphosphine)palladium(II)dichloride (94 mg, 0.13 mmol) was added to a solution of 3-(5-bromo-4-{[1-(trifluoromethyl)cyclopropyl]methyl}-1H-imidazol-2-yl)-1,1-difluoro-2-[4-(1H-pyrazol-1-yl)phenyl]propan-2-ol (202 mg, 0.45 mmol), tetramethyltin (319 mg, 1.78 mmol), lithium chloride (151 mg, 3.57 mmol), and triphenylphosphine (47 mg, 0.18 mmol) in degassed N,N-dimethylformamide (10 mL) at ambient temperature. The solution was stirred at 120° C. for 2 hr. The solution was cooled to ambient temperature and saturated aqueous potassium fluoride (10 mL) was added. The mixture was stirred for 1 hr at ambient temperature. Diethyl ether and water was added and the layers were separated. The aqueous layer was extracted with diethyl ether. The combined organic layers were washed with brine, dried (MgSO4), and concentrated in vacuo. Chromatography over C-18 silica eluting with 10-100% acetonitrile/water afforded the title compound as a white solid. 1H NMR (500 MHz, CD3OD) δ 8.22 (d, J=2.5 Hz, 1H), 7.77-7.72 (m, 2H), 7.62-7.51 (m, 3H), 6.53 (t, J=2.0 Hz, 1H), 6.14 (t, J=55.2 Hz, 1H), 3.57-3.48 (m, 2H), 2.90 (dd, J=15.7, 60.7 Hz, 2H), 2.16 (s, 3H), 0.86 (dd, J=5.0, 5.0 Hz, 2H), 0.52 (dd, J=9.5, 33.0 Hz, 2H). Individual enantiomer (E1 or E2) was obtained by HPLC separation on a chiral column.

Workup

  1. temperatureThe solution was cooled to ambient temperature
  2. stirringThe mixture was stirred for 1 hr at ambient temperature
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with diethyl ether
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-6069b9e8aede42a89e9304cd91fafb28
Source dataset
uspto-grants-2012_06
Patent number
US08193228B2

Reaction notes

Loading…