Hydrochloric Acid → HCID 22175926, compound

HRID 1797594Notes

Reaction equation

HRID 1797594 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:23])[CH3:22])[C:13]([C:24](O)=[O:25])=[C:12]2[C:27]1[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C(Cl)=O.[BH4-].[Na+].Cl>O1CCCC1.CN(C)C=O.COCCOC>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[C:15](=[O:19])[N:14]([CH2:20][CH:21]([CH3:22])[CH3:23])[C:13]([CH2:24][OH:25])=[C:12]2[C:27]1[CH:28]=[CH:29][C:30]([F:33])=[CH:31][CH:32]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 4311764Sodium borohydrideHCID 22175177HCID 22175177, compound

Product 1

HCID 22175926HCID 22175926, compoundYield 90.2%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 8028TetrahydrofuranSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 6-benzyloxy-4-(4-fluorophenyl)-2-isobutyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylic acid (3.79 g, 8.5 mmol) in tetrahydrofuran (30 mL) were added oxalyl chloride (0.9 mL, 10.2 mmol) and N,N-dimethylformamide (3 drops), and the mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in tetrahydrofuran (20 mL). The obtained solution was added dropwise to a suspension of sodium tetrahydroborate (1.13 g, 30 mmol) in 1,2-dimethoxyethane (30 mL) at 0° C. The obtained mixture was stirred at 0° C. for 1 h. The reaction mixture was poured into 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 6-benzyloxy-4-(4-fluorophenyl)-3-hydroxymethyl-2-isobutyl-1(2H)-isoquinolinone (3.31 g, 90.2%) as crystals.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. dissolutionthe residue was dissolved in tetrahydrofuran (20 mL)
  3. stirringThe obtained mixture was stirred at 0° C. for 1 h
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-05b8aef7bfeb422f983537c1b2a1b728
Source dataset
uspto-grants-2006_04
Patent number
US07034039B2

Reaction notes

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