Hydrochloric Acid → 2-(2,4-Difluorophenyl)-6-(1-hydroxy-1-methylethyl)isonicotinic acid

HRID 1909125Notes

Reaction equation

HRID 1909125 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([C:19]([CH3:21])=[CH2:20])[N:18]=1)[C:12]([O:14]C)=[O:13].[BH4-].C([N+](CC)(CC)CC)C.[OH-:32].[Na+].Cl>CO.COCCOC>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]([CH:16]=[C:17]([C:19]([OH:32])([CH3:21])[CH3:20])[N:18]=1)[C:12]([OH:14])=[O:13]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 28251Tetraethylammonium tetrahydroborate2×HCID 67339607Methyl 2-(2,4-difluorophenyl)-6-isopropenylisonicotinate

Product 1

HCID 673396622-(2,4-Difluorophenyl)-6-(1-hydroxy-1-methylethyl)isonicotinic acidYield 74.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of methyl 2-(2,4-difluorophenyl)-6-isopropenylisonicotinate (0.29 g, 1.01 mmol) in methanol (5.1 mL) and DME (5.1 mL) was added cobalt(II)mesotetraphenylporphine (6.8 mg, 10.1 mmol). The mixture was stirred at ambient temperature. After 18 h, tetraethylammonium borohydride (73.5 mg, 0.51 mmol) was added. After 15 min, additional tetraethylammonium borohydride (0.14 g, 1.01 mmol) was added. After 1.5 h, sodium hydroxide (1.0 M in water; 2.03 mL, 2.03 mmol) was added. The mixture was heated to 50° C. After 1 h, HCl (0.17 mL, 2.03 mmol) was added and the mixture was concentrated. Purification by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid) gave the title compound (0.22 g). MS 294.1 (M+1).

Workup

  1. waitAfter 15 min
  2. waitAfter 1.5 h
  3. temperatureThe mixture was heated to 50° C
  4. waitAfter 1 h
  5. concentrationthe mixture was concentrated
  6. customPurification by reverse phase chromatography (C-18, 95% water/acetonitrile→25% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-a420fb67075e4d03a90704c842265576
Source dataset
uspto-grants-2013_12
Patent number
US08598209B2

Reaction notes

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