2,6-Difluorophenylboronic acid → Methyl 3-amino-6-(2,6-difluorophenyl)picolinate

HRID 2046834Notes

Reaction equation

HRID 2046834 reaction equation
[NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5](Br)=[CH:6][CH:7]=1.[F:13][C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[C:15]=1B(O)O>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.COCCOC>[NH2:1][C:2]1[C:3]([C:9]([O:11][CH3:12])=[O:10])=[N:4][C:5]([C:15]2[C:14]([F:13])=[CH:19][CH:18]=[CH:17][C:16]=2[F:20])=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 27343362,6-Difluorophenylboronic acidHCID 45480453Methyl 3-amino-6-bromopyridine-2-carboxylate

Product 1

HCID 59226548Methyl 3-amino-6-(2,6-difluorophenyl)picolinateYield 47%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of methyl 3-amino-6-bromopicolinate (1.0 equiv.), 2,6-difluorophenyl-boronic acid (3.0 equiv), and Pd(dppf)Cl2-DCM (0.1 equiv.) in 3:1 DME/2M Na2CO3 (0.5 M) was subjected to microwave irradiation at 120° C. for 15 min intervals. The reaction was filtered and washed with EtOAc. The organic was partitioned with H2O (25 mL), was further washed with NaCl(sat.) (25 mL), was dried over MgSO4, and the volatiles were removed in vacuo. The residue was diluted in EtOAc and passed through a silica gel plug and the volatiles were removed in vacuo yielding methyl 3-amino-6-(2,6-difluorophenyl)picolinate (47%). LCMS (m/z): 265.1 (MH+); LC Rt=2.70 min

Workup

  1. customirradiation at 120° C. for 15 min intervals
  2. filtrationThe reaction was filtered
  3. washwashed with EtOAc
  4. customThe organic was partitioned with H2O (25 mL)
  5. washwas further washed with NaCl(sat.) (25 mL)
  6. dry with materialwas dried over MgSO4
  7. customthe volatiles were removed in vacuo
  8. additionThe residue was diluted in EtOAc
  9. customthe volatiles were removed in vacuo

Sources & evidence

ORD record
ord-c412311714a34ba691535b410512adbe
Source dataset
uspto-grants-2013_11
Patent number
US08592455B2

Reaction notes

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