Sodium hydride → (6-Chloro-4-iodo-5-[(2-methyl-2-propenyl)oxy]-2-pyridinyl)methanol

HRID 1072988Notes

Reaction equation

HRID 1072988 reaction equation
[Cl:1][C:2]1[C:7]([OH:8])=[C:6]([I:9])[CH:5]=[C:4]([CH2:10][OH:11])[N:3]=1.[H-].[Na+].Br[CH2:15][C:16]([CH3:18])=[CH2:17]>CN(C=O)C.CCOC(C)=O>[Cl:1][C:2]1[N:3]=[C:4]([CH2:10][OH:11])[CH:5]=[C:6]([I:9])[C:7]=1[O:8][CH2:17][C:16]([CH3:18])=[CH2:15]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 3577853-Bromo-2-methyl-1-propeneHCID 106845682-Chloro-6-(hydroxymethyl)-4-iodo-3-pyridinol

Product 1

HCID 22047031(6-Chloro-4-iodo-5-[(2-methyl-2-propenyl)oxy]-2-pyridinyl)methanolYield 86%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Chloro-6-(hydroxymethyl)-4-iodo-3-pyridinol (C2) (6.3 g, 22 mmol) is dissolved in 30 mL DMF in a dry flask under N2. The flask is placed in an ice bath, and 60% sodium hydride in mineral oil (880 mg, 22 mmol) is added. The reaction is stirred 30 min while the flask is kept in an ice bath. The ice bath is removed for 30 min and then the flask is placed back into the ice bath to cool the reaction. 3-Bromo-2-methylpropene (23.1 mmol) is added, and the reaction is stirred overnight at rt. The reaction is diluted with 150 mL EtOAc and is washed with 4×50 mL 50% saturated 1:1 NaCl/NaHCO3. The organic layer is dried over anhydrous Na2SO4, filtered, and then concentrated in vacuo to a pale oil which is crystallized from hexanes to afford (6-chloro-4-iodo-5-[(2-methyl-2-propenyl)oxy]-2-pyridinyl)methanol (C19) (86% yield). HRMS (FAB) calculated for C10H11C11NO2+H: 339.9603, found 339.9604 (M+H).

Workup

  1. customThe flask is placed in an ice bath
  2. customis kept in an ice bath
  3. customThe ice bath is removed for 30 min
  4. temperatureto cool
  5. customthe reaction
  6. stirringthe reaction is stirred overnight at rt
  7. washis washed with 4×50 mL 50% saturated 1:1 NaCl/NaHCO3
  8. dry with materialThe organic layer is dried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a pale oil which
  11. customis crystallized from hexanes

Sources & evidence

ORD record
ord-d66a2c63429342b49237d6a6ebf2d912
Source dataset
uspto-grants-2005_06
Patent number
US06911543B2

Reaction notes

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