Water → 3,5-Dichloro-2-fluoro-4-(3-isopropyl-4-hydroxyphenoxy)-6-hydroxycarbonylmethoxypyridine

HRID 352551Notes

Reaction equation

HRID 352551 reaction equation
[Cl:1][C:2]1[C:3]([F:27])=[N:4][C:5]([O:21][CH2:22][C:23]([O:25]C)=[O:24])=[C:6]([Cl:20])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15]C)=[C:11]([CH:17]([CH3:19])[CH3:18])[CH:10]=1.B(Br)(Br)Br.O>C(Cl)Cl>[Cl:1][C:2]1[C:3]([F:27])=[N:4][C:5]([O:21][CH2:22][C:23]([OH:25])=[O:24])=[C:6]([Cl:20])[C:7]=1[O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[C:11]([CH:17]([CH3:19])[CH3:18])[CH:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 25134Boron tribromideHCID 227120693,5-Dichloro-2-fluoro-4-(3-isopropyl-4-methoxyphenoxy)-6-methoxycarbonylmethoxypyridine

Product 1

HCID 227121243,5-Dichloro-2-fluoro-4-(3-isopropyl-4-hydroxyphenoxy)-6-hydroxycarbonylmethoxypyridineYield 71.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 3,5-dichloro-2-fluoro-4-(3-isopropyl-4-methoxyphenoxy)-6-methoxycarbonylmethoxy-pyridine (120 mg) in CH2Cl2 (3.0 mL) was added a solution of BBr3 in CH2Cl2 (1 mL, 1.0 M) at ambient temperature. The resulting mixture was stirred for 2 h, poured to stirring water (50 mL), extracted with CH2Cl2 (20 mL×3) from water, dried (Na2SO4) and concentrated to dryness under reduced pressure. The residue was dissolved in THF:MeOH:H2O=3:1:1 (5 mL), treated with a solution of LiOH in water (1 mL, 1.0 M) and stirred at ambient temperature for 30 min. The reaction mixture was diluted with a 1.0 M solution of HCl (50 mL), extracted with ethyl acetate(50 mL×3), dried (Na2SO4) and concentrated under reduced pressure. Purification by HPLC afforded the title compound as a colorless oil (80 mg).

Workup

  1. additionpoured
  2. extractionextracted with CH2Cl2 (20 mL×3) from water
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated to dryness under reduced pressure
  5. dissolutionThe residue was dissolved in THF
  6. additionMeOH:H2O=3:1:1 (5 mL), treated with a solution of LiOH in water (1 mL, 1.0 M)
  7. stirringstirred at ambient temperature for 30 min
  8. additionThe reaction mixture was diluted with a 1.0 M solution of HCl (50 mL)
  9. extractionextracted with ethyl acetate(50 mL×3)
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated under reduced pressure
  12. customPurification by HPLC

Sources & evidence

ORD record
ord-1f1763e450444fbf969dc576da13f1ca
Source dataset
uspto-grants-2004_06
Patent number
US06747048B2

Reaction notes

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