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

HRID 1266281Notes

Reaction equation

HRID 1266281 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 8028TetrahydrofuranSolvent3×

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 tetrahydrofuran. 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-72e0d98b99524d869ccbbfe15277ea55
Source dataset
uspto-grants-2003_04
Patent number
US06548496B2

Reaction notes

Loading…