Ethanol → 4-Chloro-6-ethoxy-7-fluoro-3-quinolinecarbonitrile

HRID 1837337Notes

Reaction equation

HRID 1837337 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[C:9]([OH:12])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]#[N:15].[C:16]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C[CH:17]=1.C(O)C.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([F:13])=[C:9]([O:12][CH2:16][CH3:17])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:14]#[N:15]

Participants

6

Reactant 4

HCID 702EthanolHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 234980764-Chloro-7-fluoro-6-hydroxy-3-quinolinecarbonitrile

Product 1

HCID 234981024-Chloro-6-ethoxy-7-fluoro-3-quinolinecarbonitrile

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. mixture of 4-chloro-7-fluoro-6-hydroxy-3-quinolinecarbonitrile (185 mg, 0.83 mmol), triphenylphosphine (392 mg, 1.49 mmol) and ethanol (153 mg, 3.32 mmol) in 15 mL of tetrahydrofuran is added diethylazodicarboxylate (260 mg, 1.80 mmol). The reaction mixture is kept at 0° C. for 45 minutes then stirred at room temperature overnight. The reaction mixture is concentrated in vacuo and purified by flash column chromatography eluting with a gradient of 1 % ethyl acetate in hexane to 5% ethyl acetate in hexane provides 4-chloro-6-ethoxy-7-fluoro-3-quinolinecarbonitrile, mp 165-166° C.

Workup

  1. concentrationThe reaction mixture is concentrated in vacuo
  2. custompurified by flash column chromatography
  3. washeluting with a gradient of 1 % ethyl acetate in hexane to 5% ethyl acetate in hexane

Sources & evidence

ORD record
ord-eea85c27c7704985b171c5b53ff0b0e0
Source dataset
uspto-grants-2004_08
Patent number
US06780996B2

Reaction notes

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