Thionyl Chloride → 1-Chloro-4-chloromethyl-3-methyl-isoquinoline

HRID 606304Notes

Reaction equation

HRID 606304 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([CH:18]=O)=[C:10]([CH3:20])[N:9]=1.O=S(Cl)[Cl:23]>C1COCC1.C(Cl)Cl>[Cl:7][C:8]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([CH2:18][Cl:23])=[C:10]([CH3:20])[N:9]=1

Participants

6

Reactant 3

HCID 24386Thionyl ChlorideHCID 21226445Aluminium lithium hydrideHCID 866159291-Chloro-3-methyl-isoquinoline-4-carbaldehyde

Product 1

HCID 866159311-Chloro-4-chloromethyl-3-methyl-isoquinolineYield 90%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

LAH (3.6 ml of 1M in THF, 3.62 mmol) is added to a solution of 1-chloro-3-methyl-isoquinoline-4-carbaldehyde (744 mg, 3.62 mmol) in THF (10 ml) at 0° C. After stirring for 30 min at ambient temperature, the mixture is quenched with small amounts of saturated sodium sulfate and filtered through a pad of celite. The filtrate is concentrated in vacuo to give the crude alcohol. SOCl2 (13 ml of 2M in DCM, 25 mmol) is added to a solution of the crude alcohol in DCM (5 ml). After stirring for 1 h at room temperature, the mixture is concentrated in vacuo and the residue is chromatographed on silica gel to give 737 mg of 1-chloro-4-chloromethyl-3-methyl-isoquinoline. 1H NMR (CDCl3) 8.44 (d, 1H), 8.18 (d, 1H), 8.02 (t, 1H), 7.82 (t, 1H), 5.03 (s, 2H), 3.00 (s, 3H).

Workup

  1. customthe mixture is quenched with small amounts of saturated sodium sulfate
  2. filtrationfiltered through a pad of celite
  3. concentrationThe filtrate is concentrated in vacuo
  4. customto give the crude alcohol
  5. stirringAfter stirring for 1 h at room temperature
  6. concentrationthe mixture is concentrated in vacuo
  7. customthe residue is chromatographed on silica gel

Sources & evidence

ORD record
ord-5c0e840b92554b8ba569216e3d66857b
Source dataset
uspto-grants-2011_03
Patent number
US07915288B2

Reaction notes

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