Acetonitrile → Tert-butyl 4-(2-cyanoacetyl)-6-fluoropyridin-3-ylcarbamate

HRID 276853Notes

Reaction equation

HRID 276853 reaction equation
[C:1](#[N:3])[CH3:2].[C:4]([O:8][C:9]([NH:11][C:12]1[C:17]([C:18]([O:20]C)=O)=[CH:16][C:15]([F:22])=[N:14][CH:13]=1)=[O:10])([CH3:7])([CH3:6])[CH3:5]>O1CCCC1>[F:22][C:15]1[N:14]=[CH:13][C:12]([NH:11][C:9](=[O:10])[O:8][C:4]([CH3:5])([CH3:6])[CH3:7])=[C:17]([C:18](=[O:20])[CH2:2][C:1]#[N:3])[CH:16]=1

Participants

4

Reactant 2

HCID 6342AcetonitrileHCID 57376998Methyl 5-[(tert-butoxycarbonyl)amino]-2-fluoropyridine-4-carboxylate

Product 1

HCID 58768582Tert-butyl 4-(2-cyanoacetyl)-6-fluoropyridin-3-ylcarbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To 140 mL of 2.5 M n-butyllithium/hexanes in 300 mL of tetrahydrofuran at −78° C. was slowly added 14.4 g of anhydrous acetonitrile in 100 mL of tetrahydrofuran. After 30 minutes was added 32 g of 5-tert-butoxycarbonylamino-2-fluoro-isonicotinic acid, methyl ester in 100 mL of tetrahydrofaran. After a further 60 minutes, the reaction was quenched with 35 mL of glacial acetic acid. The reaction was diluted with equal volumes of ethyl acetate and saturated sodium bicarbonate and the aqueous phase was washed twice with ethyl acetate. The pooled organic phases were washed with saturated sodium bicarbonate, dried, and stripped of solvent. This material was further purified by passing through a plug of silica gel with a gradient of 0-5% methanol/chloroform to give a crude product that was used as is for the following step. This material can be further purified by recrystallization from chloroform/hexanes to give a white, crystalline solid: melting point 106-115° C.; mass spectrum (m/e): M+H 279.9.

Workup

  1. customat −78° C.
  2. customthe reaction was quenched with 35 mL of glacial acetic acid
  3. additionThe reaction was diluted with equal volumes of ethyl acetate and saturated sodium bicarbonate
  4. washthe aqueous phase was washed twice with ethyl acetate
  5. washThe pooled organic phases were washed with saturated sodium bicarbonate
  6. customdried
  7. customThis material was further purified

Sources & evidence

ORD record
ord-19b7450e526a4827acbcdb956d53754c
Source dataset
uspto-grants-2002_03
Patent number
US06355636B1

Reaction notes

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