Isopropanol → 2-(3-chloro-2-(hydroxymethyl)phenyl)-6-cyclopropyl-8-fluoroisoquinolin-1(2H)-one

HRID 2069708Notes

Reaction equation

HRID 2069708 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([N:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([F:23])[CH:14]=[C:15]([CH:20]4[CH2:22][CH2:21]4)[CH:16]=3)[C:11]2=[O:24])[C:3]=1[CH:4]=[O:5].CC(O)C.[BH4-].[Na+]>C(Cl)Cl>[Cl:1][C:2]1[C:3]([CH2:4][OH:5])=[C:6]([N:10]2[CH:19]=[CH:18][C:17]3[C:12](=[C:13]([F:23])[CH:14]=[C:15]([CH:20]4[CH2:22][CH2:21]4)[CH:16]=3)[C:11]2=[O:24])[CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 3776IsopropanolHCID 4311764Sodium borohydrideHCID 594737722-chloro-6-(6-cyclopropyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)benzaldehyde

Product 1

HCID 594737982-(3-chloro-2-(hydroxymethyl)phenyl)-6-cyclopropyl-8-fluoroisoquinolin-1(2H)-oneYield 86.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-chloro-6-(6-cyclopropyl-8-fluoro-1-oxoisoquinolin-2(1H)-yl)benzaldehyde (64.6 g, 0.19 mol) was dissolved in DCM (650 ml), then, IPA (325 ml) was added to the solution. At 4° C., NaBH4 (7.15 g, 0.19 mol) was added to the reaction mixture portion wise, then the resulting solution was stirred for 1 hr. The reaction was quenched by water (170 mL), then the mixture was filtered through Celite pad. DCM layer was collected by phase separation, and DCM was distilled out and IPA was added in the same time. The desired product was crystallized out from IPA, collected by filtration, and washed with cold IPA. The filter cake was dried under vacuum at 70° C. to afford 56.3 g of the title compound (86.6% isolated yield) as a white solid. MS (ESI) 343, 345 (M+H)+.

Workup

  1. customThe reaction was quenched by water (170 mL)
  2. filtrationthe mixture was filtered through Celite pad
  3. customDCM layer was collected by phase separation, and DCM
  4. distillationwas distilled out and IPA
  5. additionwas added in the same time
  6. customThe desired product was crystallized out from IPA
  7. filtrationcollected by filtration
  8. washwashed with cold IPA
  9. customThe filter cake was dried under vacuum at 70° C.

Sources & evidence

ORD record
ord-4ef5b316c5fe40c996c4ecca005aa5f9
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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