Potassium Fluoride → Tert-butyl 2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}pyrrolidine-1-carboxylate

HRID 425407Notes

Reaction equation

HRID 425407 reaction equation
Br[C:2]1[CH:32]=[CH:31][C:5]([CH2:6][C:7]2([C:19]([NH:21][CH2:22][CH:23]([OH:30])[CH2:24][C:25]([CH3:29])([CH3:28])[CH2:26][CH3:27])=[O:20])[CH2:11][CH2:10][CH2:9][N:8]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:4][CH:3]=1.Br[C:34]1[CH:39]=[CH:38][C:37]([F:40])=[CH:36][N:35]=1.C[Sn](C)C.C[Sn](C)C.[F-].[K+]>O1CCOCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Pd]>[F:40][C:37]1[CH:38]=[CH:39][C:34]([C:2]2[CH:32]=[CH:31][C:5]([CH2:6][C:7]3([C:19]([NH:21][CH2:22][CH:23]([OH:30])[CH2:24][C:25]([CH3:28])([CH3:29])[CH2:26][CH3:27])=[O:20])[CH2:11][CH2:10][CH2:9][N:8]3[C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])=[CH:4][CH:3]=2)=[N:35][CH:36]=1

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 27831712-Bromo-5-fluoropyridineHCID 6327618HexamethylditinHCID 66705859HCID 66705859, compound

Product 1

HCID 66705703Tert-butyl 2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

Palladium tetrakis(triphenylphosphine) (1.38 g, 1.20 mmol) was added to a degassed, ambient temperature solution of tert-butyl 2-(4-bromobenzyl)-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}pyrrolidine-1-carboxylate (6.11 g, 12 mmol), 2-bromo-5-fluoropyridine (2.1 g, 12 mmol), and hexamethylditin (3.9 g, 12 mmol) in 1,4-dioxane (120 mL). After stirring at 110° C. overnight, potassium fluoride (50% on celite) was added and the solution was vigorously stirred for 1 h at ambient temperature. The mixture was filtered and the filtrate was washed with water, dried (magnesium sulfate), filtered and concentrated in vacuo. Chromatography over silica eluting with 0-50% ethyl acetate/hexane afforded tert-butyl 2-[4-(5-fluoropyridin-2-yl)benzyl]-2-{[(2-hydroxy-4,4-dimethylhexyl)amino]carbonyl}pyrrolidine-1-carboxylate.

Workup

  1. stirringthe solution was vigorously stirred for 1 h at ambient temperature
  2. filtrationThe mixture was filtered
  3. washthe filtrate was washed with water
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a1924c53fe3d48dca40fcb168284422e
Source dataset
uspto-grants-2012_01
Patent number
US08106070B2

Reaction notes

Loading…