Iodine → Tert-butyl 2-(4-(5-hydroxypicolinoyl)phenoxy)ethyl(methyl)carbamate

HRID 626159Notes

Reaction equation

HRID 626159 reaction equation
II.C(Br)C.Br[C:7]1[CH:24]=[CH:23][C:10]([O:11][CH2:12][CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:9][CH:8]=1.[OH:25][C:26]1[CH:27]=[CH:28][C:29]([C:32](N(OC)C)=[O:33])=[N:30][CH:31]=1>C1COCC1>[OH:25][C:26]1[CH:27]=[CH:28][C:29]([C:32]([C:7]2[CH:24]=[CH:23][C:10]([O:11][CH2:12][CH2:13][N:14]([CH3:22])[C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:9][CH:8]=2)=[O:33])=[N:30][CH:31]=1

Participants

6

Reactant 4

HCID 807IodineHCID 6332Ethyl BromideHCID 20785720tert-butyl N-[2-(4-bromophenoxy)ethyl]-N-methylcarbamate2×HCID 866889815-hydroxy-N-methoxy-N-methylpicolinamide

Product 1

HCID 89656144Tert-butyl 2-(4-(5-hydroxypicolinoyl)phenoxy)ethyl(methyl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
55 °C

Procedure

Mg (3.5 eq) was added to a 3-neck round bottom flask containing 50 mL anhydrous THF. The mixture was heated to 55° C. Iodine chips (2 grains) were added in one lot followed by addition of 0.1 mL ethyl bromide. Tert-butyl 2-(4-bromophenoxy)ethyl(methyl)carbamate (3.0 eq) was dissolved in 30 mL anhydrous THF, 3 mL of this solution was added at once to Mg-THF suspension. The reaction was initiated after 30 min and reflux started. The remaining solution of tert-butyl 2-(4-bromophenoxy)ethyl(methyl)carbamate was added dropwise in such speed that the reaction mixture remained reflux. After addition, the reaction mixture was further reflux for 2 h and cooled to rt. 5-Hydroxy-N-methoxy-N-methylpicolinamide (1.0 eq) in 20 mL THF was added dropwise at rt, stirred for 30 min. at rt., quenched with sat NH4Cl (aq), and extracted with EtOAc. The extract was dried, concentrated, and purified by column chromatography to give the desired product.

Workup

  1. temperaturereflux
  2. temperatureremained reflux
  3. additionAfter addition
  4. temperaturethe reaction mixture was further reflux for 2 h
  5. temperaturecooled to rt
  6. custom, quenched with sat NH4Cl (aq)
  7. extractionextracted with EtOAc
  8. customThe extract was dried
  9. concentrationconcentrated
  10. custompurified by column chromatography

Sources & evidence

ORD record
ord-26f20a740f204824b018520a262be3c4
Source dataset
uspto-grants-2016_04
Patent number
US09309211B2

Reaction notes

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