Sodium Hydroxide → 1-Chloro-6-fluoroisoquinoline

HRID 2244065Notes

Reaction equation

HRID 2244065 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N+:7]([O-])[CH:6]=[CH:5]2.P(Cl)(Cl)([Cl:15])=O.[OH-].[Na+]>C(Cl)(Cl)Cl>[Cl:15][C:8]1[C:9]2[C:4](=[CH:3][C:2]([F:1])=[CH:11][CH:10]=2)[CH:5]=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 59818249HCID 59818249, compound

Product 1

HCID 219010721-Chloro-6-fluoroisoquinolineYield 35%

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a solution of 6-fluoroisoquinoline N-oxide (3 g, 18 mmol) in CHCl3 (50 mL) is added phosphorus oxychloride (5 mL, 54 mmol). The reaction mixture is refluxed for 2 h. The reaction mixture is poured into ice, and the pH is brought to pH 8-9 with 5 M NaOH. The aqueous phase is extracted with CH2Cl2 (3×). The combined organic layers are dried over MgSO4, and evaporated. Purification of the crude product by Biotage column eluted with 0-30% EtOAc/hexanes afforded 1.06 g (35%) of 1-chloro-6-fluoro-isoquinoline. LC/MS m/z=182 [M+H]+.

Workup

  1. temperatureThe reaction mixture is refluxed for 2 h
  2. additionThe reaction mixture is poured into ice
  3. extractionThe aqueous phase is extracted with CH2Cl2 (3×)
  4. dry with materialThe combined organic layers are dried over MgSO4
  5. customevaporated
  6. customPurification of the crude product by Biotage column
  7. washeluted with 0-30% EtOAc/hexanes

Sources & evidence

ORD record
ord-51ac1780b75f4944b2d5fb3476ddede6
Source dataset
uspto-grants-2010_03
Patent number
US07678803B2

Reaction notes

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