Sodium borohydride → 5-(5-fluoro-4-hydroxymethyl-pyridin-3-yl)-3H-isobenzofuran-1-one

HRID 1897612Notes

Reaction equation

HRID 1897612 reaction equation
[F:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[C:15](=[O:19])[O:14][CH2:13]3)[C:7]=1[CH:8]=[O:9].[BH4-].[Na+]>CO>[F:1][C:2]1[C:7]([CH2:8][OH:9])=[C:6]([C:10]2[CH:11]=[C:12]3[C:16](=[CH:17][CH:18]=2)[C:15](=[O:19])[O:14][CH2:13]3)[CH:5]=[N:4][CH:3]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 866748373-Fluoro-5-(1-oxo-1,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde

Product 1

HCID 671549685-(5-fluoro-4-hydroxymethyl-pyridin-3-yl)-3H-isobenzofuran-1-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To 3-fluoro-5-(1-oxo-1,3-dihydro-isobenzofuran-5-yl)-pyridine-4-carbaldehyde (180 mg, 0.700 mmol) in MeOH (7 mL) at 0° C. was added sodium borohydride (39.7 mg, 1.050 mmol). The reaction mixture was stirred at room temperature for 30 min. The reaction was quenched with water and extracted with DCM twice. The organic layer was dried over sodium sulfate and concentrated in vacuo. The crude was dissolved in MeOH (10 mL) and purified on HPLC using RP18 column and gradient 0.1% aqueous NH4OH in acetonitrile to afford 5-(5-fluoro-4-hydroxymethyl-pyridin-3-yl)-3H-isobenzofuran-1-one. 1H NMR (400 MHz, MeOD) δ ppm 4.62 (d, J=1.5 Hz, 2H), 5.51 (s, 2H), 7.78 (d, J=7.8 Hz, 1H), 7.82 (s, 1H), 8.04 (d, J=7.8 Hz, 1H), 8.46 (s, 1H), 8.59 (d, J=1.5 Hz, 1H); HRMS: (ESI) m/z 260.0735 [(M+H)+ Calcd for C14H10FNO3 260.0723].

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with DCM twice
  3. dry with materialThe organic layer was dried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude was dissolved in MeOH (10 mL)
  6. custompurified on HPLC

Sources & evidence

ORD record
ord-17ed7ef6d87749cbb6e68ab0e101c8e3
Source dataset
uspto-grants-2013_08
Patent number
US08519134B2

Reaction notes

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