Thionyl Chloride → HCID 68295546, compound

HRID 572524Notes

Reaction equation

HRID 572524 reaction equation
[CH3:1][C:2]1[CH:7]=[C:6]([CH3:8])[CH:5]=[CH:4][C:3]=1[C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=2)[C:12](=[O:19])[N:11]([CH3:20])[C:10]=1[C:21](O)=O.S(Cl)([Cl:26])=O.[BH4-].[Na+]>CO>[Cl:26][CH2:21][C:10]1[N:11]([CH3:20])[C:12](=[O:19])[C:13]2[C:18]([C:9]=1[C:3]1[CH:4]=[CH:5][C:6]([CH3:8])=[CH:7][C:2]=1[CH3:1])=[CH:17][CH:16]=[CH:15][CH:14]=2

Participants

5

Reactant 3

HCID 24386Thionyl ChlorideHCID 4311764Sodium borohydrideHCID 68294980HCID 68294980, compound

Product 1

HCID 68295546HCID 68295546, compoundYield 76%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

A suspension of 4-(2,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydroisoquinoline-3-carboxylic acid (21.6 g) in thionyl chloride (218 mL, 2987 mmol) was heated at 70° C. for 2 hours. The mixture was concentrated, dissolved in tetrahydrofuran (THF) (15 mL), and treated with sodium borohydride (0.929 g, 24.56 mmol). The resulting mixture was heated to 70° C. for 2 hours until LCMS indicated complete reaction. The mixture was cooled to 0° C. and methanol was added until gas evolution ceased. The mixture was concentrated, diluted with water and then extracted three times with dichloromethane. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was treated with thionyl chloride (20 mL) and heated at 70° C. for 2 hours. The mixture was concentrated and then purified on silica gel (0-70% EA/Hexane) to afford the title compound (1.17 g, 76%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.46-8.59 (m, 1 H) 7.47-7.57 (m, 2 H) 7.05-7.24 (m, 3 H) 6.87-6.99 (m, 1 H) 4.43-4.55 (m, 1 H) 4.31-4.41 (m, 1 H) 3.86 (s, 3 H) 2.43 (s, 3 H) 2.01 (s, 3 H). LC/MS (m/z) ES+=312 (M+1).

Workup

  1. concentrationThe mixture was concentrated
  2. dissolutiondissolved in tetrahydrofuran (THF) (15 mL)
  3. temperatureThe resulting mixture was heated to 70° C. for 2 hours until LCMS
  4. customreaction
  5. temperatureThe mixture was cooled to 0° C.
  6. concentrationThe mixture was concentrated
  7. additiondiluted with water
  8. extractionextracted three times with dichloromethane
  9. washThe combined extracts were washed with brine
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. additionThe residue was treated with thionyl chloride (20 mL)
  14. temperatureheated at 70° C. for 2 hours
  15. concentrationThe mixture was concentrated
  16. custompurified on silica gel (0-70% EA/Hexane)

Sources & evidence

ORD record
ord-8ca060ef96584e62915dedac44983ceb
Source dataset
uspto-grants-2015_05
Patent number
US09029391B2

Reaction notes

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