Diisopropylethylamine → Methyl 5-(3-fluorobenzyl)picolinate

HRID 1777539Notes

Reaction equation

HRID 1777539 reaction equation
[F:1][C:2]1[CH:3]=[C:4](B(O)O)[CH:5]=[CH:6][CH:7]=1.Br[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]([O:21][CH3:22])=[O:20])=[N:17][CH:18]=1.C(N(CC)C(C)C)(C)C>C(COC)OC.O.[Pd].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>[F:1][C:2]1[CH:3]=[C:4]([CH:5]=[CH:6][CH:7]=1)[CH2:12][C:13]1[CH:14]=[CH:15][C:16]([C:19]([O:21][CH3:22])=[O:20])=[N:17][CH:18]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 27339863-Fluorophenylboronic acidHCID 19699469Methyl 5-(bromomethyl)pyridine-2-carboxylate

Product 1

HCID 67974406Methyl 5-(3-fluorobenzyl)picolinateYield 264.2%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

A mixture of 3-fluorophenylboronic acid (0.319 g; 2.28 mmol), methyl 5-(bromomethyl)picolinate (0.350 g; 0.230 mmol), tetrakis-(triphenylphosphine)-palladium(0) (0.175; 0.152 mmol) and N,N diisopropylethylamine (0.524 g; 3.04 mmol) in dimethoxyethane (9 mL) and water (3 mL) was irradiated in a microwave oven at 130° C. for 20 minutes. The resulting solution was partitioned between water and ethyl acetate. The organic layer was separated and concentrated under reduced pressure. The crude residue was purified by flash chromatography on silica gel (eluent 1 to 10% ethyl acetate in dichlomethane) to afford 0.149 g (40%) of the title compound as a yellow oil.

Workup

  1. customwas irradiated in a microwave oven at 130° C. for 20 minutes
  2. customThe resulting solution was partitioned between water and ethyl acetate
  3. customThe organic layer was separated
  4. concentrationconcentrated under reduced pressure
  5. customThe crude residue was purified by flash chromatography on silica gel (eluent 1 to 10% ethyl acetate in dichlomethane)

Sources & evidence

ORD record
ord-194953a6edf845e894921923b3018298
Source dataset
uspto-grants-2016_02
Patent number
US09266832B2

Reaction notes

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