Cyclopropylboronic acid → 3-Amino-6-cyclopropyl-5-(trifluoromethyl)picolinic acid

HRID 2202522Notes

Reaction equation

HRID 2202522 reaction equation
C[O:2][C:3]([C:5]1[C:10]([NH2:11])=[CH:9][C:8]([C:12]([F:15])([F:14])[F:13])=[C:7](Br)[N:6]=1)=[O:4].[CH:17]1(B(O)O)[CH2:19][CH2:18]1>C1COCC1>[NH2:11][C:10]1[C:5]([C:3]([OH:2])=[O:4])=[N:6][C:7]([CH:17]2[CH2:19][CH2:18]2)=[C:8]([C:12]([F:15])([F:14])[F:13])[CH:9]=1

Participants

4

Reactant 2

HCID 2760897Cyclopropylboronic acidHCID 58964428Methyl 3-amino-6-bromo-5-(trifluoromethyl)picolinate2×

Product 1

HCID 584423273-Amino-6-cyclopropyl-5-(trifluoromethyl)picolinic acid

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A microwave vial was charged with amino-6-bromo-5-trifluoromethyl-pyridine-2-carboxylic acid methyl ester (Intermediate A4) (0.5 g, 1.754 mmol), cyclopropylboronic acid (0.753 g, 8.77 mmol), and 1,1′Bis(diphenylphosphosphino)ferrocene palladium dichloride (0.143 g, 0.175 mmol). The mixture was taken up as a solution in THF (6 ml) and flushed with N2, sealed and heated using microwave radiation at 150° C. for 20 minutes. The reaction mixture was filtered through Celite® (filter material) and washed through with EtOAc (20 ml). The filtrate was partitioned between EtOAc (30 ml) and water (50 ml). The phases were separated and the organic portion was washed with brine (30 ml), dried over MgSO4, filtered and concentrated under vacuum.

Workup

  1. customflushed with N2
  2. customsealed
  3. temperatureheated
  4. customat 150° C.
  5. customfor 20 minutes
  6. filtrationThe reaction mixture was filtered through Celite® (filter material)
  7. washwashed through with EtOAc (20 ml)
  8. customThe filtrate was partitioned between EtOAc (30 ml) and water (50 ml)
  9. customThe phases were separated
  10. washthe organic portion was washed with brine (30 ml)
  11. dry with materialdried over MgSO4
  12. filtrationfiltered
  13. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-115f62c7223c4e56ada917d3f6ecfd11
Source dataset
uspto-grants-2016_06
Patent number
US09365552B2

Reaction notes

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