1,2-Dimethoxyethane → Methyl 4-amino-6-(4-chlorophenyl)-3-methoxypicolinate

HRID 407215Notes

Reaction equation

HRID 407215 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6](Br)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[O:13][CH3:14].COCCOC.[Cl:21][C:22]1[CH:27]=[CH:26][C:25](B2OCCCO2)=[CH:24][CH:23]=1.[F-].[Cs+]>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[NH2:1][C:2]1[CH:7]=[C:6]([C:25]2[CH:26]=[CH:27][C:22]([Cl:21])=[CH:23][CH:24]=2)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[C:3]=1[O:13][CH3:14]

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 25953Cesium fluorideHCID 34689572-(4-Chlorophenyl)-1,3,2-dioxaborinaneHCID 21696668Methyl 4-amino-6-bromo-3-methoxypicolinate

Product 1

HCID 71150624Methyl 4-amino-6-(4-chlorophenyl)-3-methoxypicolinateYield 44%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
110 °C

Procedure

To a solution of methyl 4-amino-6-bromo-3-methoxypicolinate (prepared as in Fields, S. C. et al. U.S. Pat. No. 6,297,197 B1, Oct. 2, 2001; 500 mg, 1.9 mmol) in a 1:1 mixture of DME (4.5 mL) and H2O (4.5 mL) was added 2-(4-chlorophenyl)-1,3,2-dioxaborinane (561 mg, 2.7 mmol), CsF (288 mg, 1.9 mmol) and PdCl2(PPh3)2 (26 mg, 0.1941 mmol). The reaction was heated at 110° C. in a CES microwave for 20 min. The reaction mixture was cooled to ambient temperature and diluted with CH2Cl2, then washed with water, satd aq NaHCO3 and satd aq NaCl. The organic layer was dried with Na2SO4 and filtered. The solvent was removed in vacuo. The residue was purified by normal phase chromatography (eluting with 5% Et2O in CH2Cl2 with 0.05% acetic acid (HOAc)) to afford the title compound as a brown oil (245 mg, 44%): 1H NMR (300 MHz, CDCl3) δ 7.90-7.81 (m, 2H), 7.46-7.36 (m, 2H), 7.12 (s, 1H), 4.56 (s, 2H), 4.01 (s, 3H), 3.92 (s, 3H), ESIMS m/z 291 ([M−H]−).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. washwashed with water
  3. dry with materialThe organic layer was dried with Na2SO4
  4. filtrationfiltered
  5. customThe solvent was removed in vacuo
  6. customThe residue was purified by normal phase chromatography (eluting with 5% Et2O in CH2Cl2 with 0.05% acetic acid (HOAc))

Sources & evidence

ORD record
ord-d9bddad0f61c4df48dfb937e78e13d44
Source dataset
uspto-grants-2014_06
Patent number
US08754229B2

Reaction notes

Loading…