Sodium hydride → HCID 89739180, compound

HRID 2206615Notes

Reaction equation

HRID 2206615 reaction equation
[OH:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH3:11])[N:5]=[C:4]([CH3:12])[CH:3]=1.[H-].[Na+].Cl[C:16]([F:23])([F:22])C(OCC)=O>CN(C)C=O>[F:22][CH:16]([F:23])[O:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([O:10][CH3:11])[N:5]=[C:4]([CH3:12])[CH:3]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 67843Acetic acid, 2-chloro-2,2-difluoro-, ethyl esterHCID 178494181HCID 178494181, compound

Product 1

HCID 89739180HCID 89739180, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-hydroxy-2-methoxy-6-methylnicotinonitrile (2.0 g, 12.2 mmol) in N,N-dimethylformamide (10 mL) was added sodium hydride (880 mg, 36.6 mmol) at 0° C. and the mixture was stirred for 0.5 hour, Ethyl 2-chloro-2,2-difluoroacetate (5.4 g, 39.0 mmol) was added with vigorous stirring, over the course of 20 min. The suspension was warmed to 80° C. overnight under N2. The mixture was quenched into Na2CO3 (200 mL). It was partitioned between water (500 mL) and ethyl acetate (500 mL), the organic layer was dried and concentrated to afford the crude, which was purified by flash column (PE:EA=20:1) to afford 4-(difluoromethoxy)-2-methoxy-6-methylnicotinonitrile (550 mg yellow solid, 22.0% yield).

Workup

  1. customThe mixture was quenched into Na2CO3 (200 mL)
  2. customIt was partitioned between water (500 mL) and ethyl acetate (500 mL)
  3. customthe organic layer was dried
  4. concentrationconcentrated
  5. customto afford the crude, which
  6. customwas purified by flash column (PE:EA=20:1)

Sources & evidence

ORD record
ord-6af7841f3ec84f0e95ac08d829c79f25
Source dataset
uspto-grants-2016_06
Patent number
US09371331B2

Reaction notes

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