Potassium Fluoride → 1-Tert-butyl 2-methyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]pyrrolidine-1,2-dicarboxylate

HRID 425412Notes

Reaction equation

HRID 425412 reaction equation
Br[C:2]1[CH:26]=[CH:25][C:5]([CH2:6][C:7]2([C:21]([O:23][CH3:24])=[O:22])[CH2:11][C:10]([F:13])([F:12])[CH2:9][N:8]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:4][CH:3]=1.Br[C:28]1[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=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:12][C:10]1([F:13])[CH2:9][N:8]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C:7]([CH2:6][C:5]2[CH:25]=[CH:26][C:2]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][N:29]=3)=[CH:3][CH:4]=2)([C:21]([O:23][CH3:24])=[O:22])[CH2:11]1

Participants

7

Reactant 4

HCID 522689Potassium FluorideHCID 27831712-Bromo-5-fluoropyridineHCID 6327618HexamethylditinHCID 667056321-Tert-butyl 2-methyl 2-(4-bromobenzyl)-4,4-difluoropyrrolidine-1,2-dicarboxylate

Product 1

HCID 667056021-Tert-butyl 2-methyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]pyrrolidine-1,2-dicarboxylate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

Palladium tetrakis(triphenylphosphine) (169 mg, 0.15 mmol) was added to a degassed, ambient temperature solution of 1-tert-butyl 2-methyl 2-(4-bromobenzyl)-4,4-difluoropyrrolidine-1,2-dicarboxylate (634 mg, 1.46 mmol), 2-bromo-5-fluoropyridine (257 mg, 1.46 mmol), and hexamethylditin (478 mg, 1.46 mmol) in 1,4-dioxane (5 mL). After stirring at 110° C. overnight, potassium fluoride (50% on celite) was added. After stirring vigorously for a further 1 h, the reaction mixture was filtered, washed with water, dried (magnesium sulfate), filtered and concentrated in vacuo. Chromatography over silica eluting with 0-50% ethyl acetate/hexane afforded 1-tert-butyl 2-methyl 4,4-difluoro-2-[4-(5-fluoropyridin-2-yl)benzyl]pyrrolidine-1,2-dicarboxylate.

Workup

  1. stirringAfter stirring vigorously for a further 1 h
  2. filtrationthe reaction mixture was filtered
  3. washwashed with water
  4. dry with materialdried (magnesium sulfate)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-757b00713be64b5fa933ccfac2655d36
Source dataset
uspto-grants-2012_01
Patent number
US08106070B2

Reaction notes

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