2-Methyl-2-butene → HCID 86723413, compound
Reaction equation
[NH2:1][C:2]1[C:7]([F:8])=[C:6]([CH2:9][C:10]2[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=2)[N:5]=[C:4]([CH:17]=[O:18])[C:3]=1[Cl:19].CC(=CC)C.P([O-])([O-])(O)=[O:26].[Na+].[Na+].Cl([O-])=O.[Na+]>O.C(O)(C)(C)C>[NH2:1][C:2]1[C:7]([F:8])=[C:6]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([F:16])=[CH:14][CH:15]=2)[N:5]=[C:4]([C:17]([OH:26])=[O:18])[C:3]=1[Cl:19]Participants
Conditions
- Temperature
- 70 °C
Procedure
A microwave vial equipped with a magnetic stir bar was charged with 4-amino-3-chloro-5-fluoro-6-(4-fluorobenzyl)picolinaldehyde (280 mg, 0.991 mmol) and t-butanol (4.95 mL). The mixture was treated with H2O (1.651 mL), 2-methylbut-2-ene (0.94 mL, 0.991 mmol), sodium hydrogenphosphate (281 mg, 1.981 mmol), and finally sodium chlorite (269 mg, 2.97 mmol) was added in one portion. The mixture was heated to 70° C. in the microwave for 2 h. An aliquot of the reaction mixture was analyzed by LC-MS. LC-MS analysis showed one major product with the correct mass for the desired product. The reaction mixture was diluted with EtOAc (15 mL) and washed with 1 M HCl (1×5 mL), H2O (1×5 mL) and saturated NaCl (1×5 mL). The organic phase was dried (Na2SO4), filtered and concentrated in vacuo. The crude material was stirred with Et2O (5 mL). After stiffing, the solid was removed by vacuum filtration washing with Et2O. The solid was air-dried for several hours and then dried under vacuum. 4-Amino-3-chloro-5-fluoro-6-(4-fluorobenzyl)picolinic acid (40 mg, 12.84%) was isolated as an off-white solid: 1H NMR (400 MHz, CDCl3) δ 11.60 (s, 1H), 7.22 (m, 2H), 7.00 (m, 2H), 5.03 (s, 2H), 4.08 (m, 2H); 19F NMR (376 MHz, CDCl3) δ −115.76, −139.38; ESIMS m/z 297 ([M−H]−).
Workup
- customA microwave vial equipped with a magnetic stir bar
- additionwas added in one portion
Sources & evidence
- ORD record
- ord-b6178e0d431a41788874a9ece08982bf
- Source dataset
- uspto-grants-2015_08
- Patent number
- US09096526B2
Reaction notes
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