Sodium hydride → Methyl 5-chloro-6-[(1,3-difluoropropan-2-yl)oxy]nicotinate

HRID 217468

Reaction equation

HRID 217468 reaction equation
[Cl:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[H-].[Na+].[F:15][CH2:16][CH:17]([OH:20])[CH2:18][F:19]>C1COCC1>[Cl:1][C:2]1[C:3]([O:20][CH:17]([CH2:18][F:19])[CH2:16][F:15])=[N:4][CH:5]=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 679851,3-Difluoro-2-propanolHCID 2782166Methyl 5,6-Dichloronicotinate

Product 1

HCID 67363966Methyl 5-chloro-6-[(1,3-difluoropropan-2-yl)oxy]nicotinateYield 80.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Methyl 5,6-dichloronicotinate (1.5 g) and 60% sodium hydride (640 mg) were dissolved in THF (45 mL). 1,3-Difluoropropan-2-ol (1.5 g) was added thereto at 0° C., followed by stirring at 0° C. for 3 hours, and the reaction solution was quenched with aqueous NH4Cl. After extraction with EtOAc, the organic layer was dried over MgSO4 and then filtered, and the desiccant was removed. The vehicle was evaporated under reduced pressure, followed by purification by silica gel column chromatography (hexane:AcOEt=100:0 to 50:50) to obtain methyl 5-chloro-6-[(1,3-difluoropropan-2-yl)oxy]nicotinate (1.56 g) as a colorless liquid.

Workup

  1. customat 0° C.
  2. customthe reaction solution was quenched with aqueous NH4Cl
  3. extractionAfter extraction with EtOAc
  4. dry with materialthe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. customthe desiccant was removed
  7. customThe vehicle was evaporated under reduced pressure
  8. customfollowed by purification by silica gel column chromatography (hexane:AcOEt=100:0 to 50:50)

Sources & evidence

ORD record
ord-6d3346eb5732435ab3e1c1b3e3aff310
Source dataset
uspto-grants-2012_06
Patent number
US08193378B2

Linked notes

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