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

HRID 505564Notes

Reaction equation

HRID 505564 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].[N:20]1C=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]([NH2:20])=[N:8][CH:9]=[CH:10][C:11]=1[CH3:12]

Participants

7

Reactant 4

HCID 1049PyridineHCID 6386tert-ButanolHCID 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 (2 g, 5.84 mmol) in THF (12 mL) was added TEA (1.627 mL, 11.68 mmol), pyridine (944 ul, 11.68 mmol), t-butanol (2.79 mL, 29.2 mmol) and diphenylphosphoryl azide (1.89 mL, 8.76 mmol). The resulting mixture was heated to 65° C. for 35 minutes, after which the mixture was diluted with CH2Cl2 (2×100 mL) and washed with water (100 mL). The combined organic extracts were concentrated in vacuo, and the resulting residue was dissolved in TFA (20 mL) and allowed to stand for 15 minutes. After this time, the solvent was removed in vacuo and the residue was partitioned between saturated aqueous NaHCO3 (50 mL) and CH2Cl2 (100 mL). The organic extract was 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 in vacuo
  3. dissolutionthe resulting residue was dissolved in TFA (20 mL)
  4. customAfter this time, the solvent was removed in vacuo
  5. customthe residue was partitioned between saturated aqueous NaHCO3 (50 mL) and CH2Cl2 (100 mL)
  6. extractionThe organic extract
  7. concentrationwas concentrated on the rotary evaporator
  8. customthe residue was purified
  9. washeluting with a gradient of 0-30% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-15dc1b0e33fe44db90a70a48be0c06e5
Source dataset
uspto-grants-2010_08
Patent number
US07781454B2

Reaction notes

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