Sodium borohydride → 6-(tert-butyl)-2-(3-chloro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-one

HRID 1185024Notes

Reaction equation

HRID 1185024 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:18]=1[CH:19]=[O:20])[N:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[BH4-].[Na+]>C(Cl)Cl>[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:15])[CH:14]=1)[C:11](=[O:16])[N:10]([C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[C:18]=1[CH2:19][OH:20])[N:9]=[CH:8]2)([CH3:4])([CH3:2])[CH3:3]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 594738282-(6-(tert-butyl)-8-fluoro-1-oxophthalazin-2(1H)-yl)-6-chlorobenzaldehyde

Product 1

HCID 594737806-(tert-butyl)-2-(3-chloro-2-(hydroxymethyl)phenyl)-8-fluorophthalazin-1(2H)-oneYield 76.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-(6-tert-Butyl-8-fluoro-1-oxo-1H-phthalazin-2-yl)-6-chloro-benzaldehyde 101i (519 mg, 1.4 mmol) was dissolved in DCM (2 mL) with stirring at room temperature, and then 1 mL of iPA was added to the solution. The resulting solution was cooled to 4° C., and NaBH4 (27 mg, 0.7 mmol) was added in one portion. After 30 min stirring, the reaction was quenched by adding H2O (2 mL). The aqueous layer was extracted with CH2Cl2 (2×5 mL), washed with brine and dried over MgSO4. The filtrate was concentrated to give a residue which was purified by silica gel chromatography eluting with 0-20% EtOAc/CH2Cl2 to furnish 101j as a white solid (385 mg, 72%). MS: [M+H]+: 361

Workup

  1. addition1 mL of iPA was added to the solution
  2. temperatureThe resulting solution was cooled to 4° C.
  3. stirringAfter 30 min stirring
  4. customthe reaction was quenched
  5. additionby adding H2O (2 mL)
  6. extractionThe aqueous layer was extracted with CH2Cl2 (2×5 mL)
  7. washwashed with brine
  8. dry with materialdried over MgSO4
  9. concentrationThe filtrate was concentrated
  10. customto give a residue which
  11. customwas purified by silica gel chromatography
  12. washeluting with 0-20% EtOAc/CH2Cl2

Sources & evidence

ORD record
ord-dff29ef29a2c464dad350ffeb60c4905
Source dataset
uspto-grants-2014_03
Patent number
US08669251B2

Reaction notes

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