Pyridine → 3-(3-Bromo-5-chlorophenoxy)-4-methylpyridin-2-amine

HRID 1952350Notes

Reaction equation

HRID 1952350 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:7](C(O)=O)=[N:8][CH:9]=[CH:10][C:11]=1[CH3:12].C([N:22](CC)CC)C.N1C=CC=CC=1.C(O)(C)(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>C1COCC1.C(Cl)Cl>[Br:1][C:2]1[CH:3]=[C:4]([CH:16]=[C:17]([Cl:19])[CH:18]=1)[O:5][C:6]1[C:7]([NH2:22])=[N:8][CH:9]=[CH:10][C:11]=1[CH3:12]

Participants

8

Reactant 5

HCID 1049PyridineHCID 6386tert-ButanolHCID 8471TriethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 684271923-(3-Bromo-5-chlorophenoxy)-4-methylpyridine-2-carboxylic acid

Product 1

HCID 684265783-(3-Bromo-5-chlorophenoxy)-4-methylpyridin-2-amine

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
65 °C

Procedure

To a suspension of 3-(3-bromo-5-chlorophenoxy)-4-methylpyridine-2-carboxylic acid (11-3; 2 g, 5.84 mmol) in THF (12 mL) was added triethylamine (1.627 mL, 11.68 mmol), pyridine (944 μL, 11.68 mmol), t-butanol (2.79 mL, 29.2 mmol) and diphenylphosphoryl azide (1.89 mL, 8.76 mmol) and the mixture heated to 65° C. for 35 minutes. After this time, the reaction mixture was diluted with CH2Cl2 (2×100 mL) and washed with water (100 mL). The combined organic extracts were concentrated to an oil on a rotary evaporator. This residue was dissolved in trifluoroacetic acid (20 mL) and allowed to stand for 15 minutes. After this time, the solvent was removed in vacuo and the residue was partitioned between CH2Cl2 (2×100 mL) and saturated aqueous NaHCO3 (50 mL). The combined extracts were concentrated on the rotary evaporator and the residue was purified using a RediSep column (330 g) eluting with a gradient of 0-30% EtOAc/CH2Cl2 to give the title compound. LRMS (M+1)=314.9.

Workup

  1. washwashed with water (100 mL)
  2. concentrationThe combined organic extracts were concentrated to an oil on a rotary evaporator
  3. dissolutionThis residue was dissolved in trifluoroacetic acid (20 mL)
  4. customAfter this time, the solvent was removed in vacuo
  5. customthe residue was partitioned between CH2Cl2 (2×100 mL) and saturated aqueous NaHCO3 (50 mL)
  6. concentrationThe combined extracts were concentrated on the rotary evaporator
  7. customthe residue was purified
  8. washeluting with a gradient of 0-30% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-e785ed025372411bb17db6c6c6e69aa1
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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