Iodine → 5-iodo-3-[(R) 1-(2.6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamine

HRID 1627522Notes

Reaction equation

HRID 1627522 reaction equation
I(O)(=O)(=O)=O.[I:6]I.S(=O)(=O)(O)O.[Cl:13][C:14]1[C:19]([F:20])=[CH:18][CH:17]=[C:16]([Cl:21])[C:15]=1[C@H:22]([O:24][C:25]1[C:26]([NH2:31])=[N:27][CH:28]=[CH:29][CH:30]=1)[CH3:23]>C(O)(=O)C.O>[I:6][C:29]1[CH:30]=[C:25]([O:24][C@@H:22]([C:15]2[C:16]([Cl:21])=[CH:17][CH:18]=[C:19]([F:20])[C:14]=2[Cl:13])[CH3:23])[C:26]([NH2:31])=[N:27][CH:28]=1

Participants

7

Reactant 4

HCID 807IodineHCID 1118Sulfuric AcidHCID 65185Metaperiodic acidHCID 49765905(R)-3-(1-(2,6-Dichloro-3-fluorophenyl)ethoxy)pyridin-2-amine

Product 1

HCID 115028055-iodo-3-[(R) 1-(2.6-dichloro-3-fluoro-phenyl)-ethoxy]-pyridin-2-ylamineYield 120%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

Periodic acid (60 mg, 0.24 mmol), iodine (130 mg, 0.5 mmol), and sulfuric acid (0.03 mL) were added sequentially to a stirred solution of 3-[(1R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]pyridin-2-amine (0.97 mmol) in a mixture of acetic acid (3 mL) and H2O (0.5 mL). The resulting solution was heated to 80° C. for 5 h. The cooled reaction mixture was quenched with Na2SO3 (80 mg) and basicified with saturated Na2CO3 (2×100 mL) to pH 7. CH2Cl2 (2×50 mL) was added to extract the aqueous solution. The combined organic layers were dried over Na2SO4 then filtered and concentrated under vacuum. The residue was purified by flash chromatography (eluting with 35→40% EtOAc in hexanes) to give the title compound as a yellow oil (254 mg; 0.6 mmol; 61.6% yield); MS (APCI) (M+H)+ 426. 1H NMR (400 MHz, chloroform-D) δ ppm 1.81 (d, J=6.8 Hz, 3H) 4.86 (s, 2H) 5.98 (q, J=6.57 Hz, 1H) 6.96 (d, J=1.5 Hz, 1H) 7.08 (dd, J=9.0, 8.0 Hz, 1H) 7.31 (dd, J=8.8, 4.8 Hz, 1H) 7.78 (d, J=1.8 Hz, 1H).

Workup

  1. customThe cooled reaction mixture
  2. customwas quenched with Na2SO3 (80 mg)
  3. additionCH2Cl2 (2×50 mL) was added
  4. extractionto extract the aqueous solution
  5. dry with materialThe combined organic layers were dried over Na2SO4
  6. filtrationthen filtered
  7. concentrationconcentrated under vacuum
  8. customThe residue was purified by flash chromatography (eluting with 35→40% EtOAc in hexanes)

Sources & evidence

ORD record
ord-29aa1ee33ad5466a9a8d4c9e37265c97
Source dataset
uspto-grants-2014_07
Patent number
US08785632B2

Reaction notes

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