Methanol → Methyl 4-amino-6-(4-ethynylphenyl)-5-fluoro-3-methoxypicolinate

HRID 407236Notes

Reaction equation

HRID 407236 reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([CH:15]=O)=[CH:11][CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:3]=1[O:21][CH3:22].[C:23]([O-])([O-])=O.[K+].[K+].CO.[N+](=C(P(=O)(OC)OC)C(=O)C)=[N-]>CCOCC>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([C:9]2[CH:14]=[CH:13][C:12]([C:15]#[CH:23])=[CH:11][CH:10]=2)[N:5]=[C:4]([C:17]([O:19][CH3:20])=[O:18])[C:3]=1[O:21][CH3:22]

Participants

6

Reactant 4

HCID 887MethanolHCID 11430Potassium CarbonateHCID 86675410Methyl 4-amino-5-fluoro-6-(4-formylphenyl)-3-methoxypicolinateHCID 136023029(1E)-1-diazo-1-dimethoxyphosphorylpropan-2-one

Product 1

HCID 86675411Methyl 4-amino-6-(4-ethynylphenyl)-5-fluoro-3-methoxypicolinateYield 73.4%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Procedure

To a 20 mL reaction vial were added methyl 4-amino-5-fluoro-6-(4-formylphenyl)-3-methoxypicolinate (0.41 g, 1.347 mmol), K2CO3 (0.372 g, 2.69 mmol), and CH3OH (20 mL). Dimethyl 1-diazo-2-oxopropylphosphonate (0.311 g, 1.617 mmol) was added in one portion. After stirring for 4 h, the reaction mixture was diluted with Et2O (50 mL) and washed with 5% NaHCO3 (25 mL). The organic layer was dried over MgSO4 (5 g), filtered, and concentrated on a rotary evaporator. The resulting residue was purified using a Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc to yield the title compound as an off-white solid (297 mg, 73%): 1H NMR (400 MHz, CDCl3) δ 7.93-7.85 (m, 2H), 7.62-7.53 (m, 2H), 4.57 (s, 2H), 3.98 (s, 3H), 3.96 (s, 3H), 3.15 (s, 1H); 19F NMR (376 MHz, CDCl3) δ −139.97; ESIMS m/z 301 ([M+H]+), 299 ([M−H]−).

Workup

  1. customTo a 20 mL reaction
  2. washwashed with 5% NaHCO3 (25 mL)
  3. dry with materialThe organic layer was dried over MgSO4 (5 g)
  4. filtrationfiltered
  5. concentrationconcentrated on a rotary evaporator
  6. customThe resulting residue was purified
  7. customa Teledyne ISCO purification system with a gradient eluent system of CH2Cl2 and EtOAc

Sources & evidence

ORD record
ord-d264d639e2c34700859c2d2a5fba941e
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

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