Sodium borohydride → Methyl 2-chloro-6-(hydroxymethyl)nicotinate

HRID 2063987Notes

Reaction equation

HRID 2063987 reaction equation
[Cl-].[Ca+2].[Cl-].[BH4-].[Na+].C[O:7][C:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]([O:18][CH3:19])=[O:17])=[C:12]([Cl:20])[N:11]=1)=O>C(O)C.C1COCC1>[CH3:19][O:18][C:16](=[O:17])[C:13]1[CH:14]=[CH:15][C:10]([CH2:8][OH:7])=[N:11][C:12]=1[Cl:20]

Participants

6

Reactant 3

HCID 4311764Sodium borohydrideHCID 5284359Calcium ChlorideHCID 583245856-Chloro-pyridine-2,5-dicarboxylic acid dimethyl ester

Product 1

HCID 59140116Methyl 2-chloro-6-(hydroxymethyl)nicotinateYield 69.2%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A cold (0° C.) suspension of calcium chloride (19.54 g, 176 mmol) and sodium borohydride (4.18 g, 110 mmol) in anhydrous ethanol (176 mL) and anhydrous THF (88 mL) was stirred for 1 hour, after which 6-chloro-pyridine-2,5-dicarboxylic acid dimethyl ester (9.97 g, 44 mmol) was added. After stirring at 0° C. for a further 6 hours, the reaction was quenched by the addition of H2SO4 (35 mL, 5M). The reaction mixture was diluted with ethyl acetate and filtered through Celite®. The filtrate was washed with 1M NaOH, water and brine, the organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo. The resultant residue was subjected to flash chromatography (Si-PPC, gradient 0% to 100%, ethyl acetate in hexane) to afford the title compound as a yellow oil (6.14 g, 69%). LCMS (method B): RT=2.34 min, [M+H]+=202.

Workup

  1. stirringAfter stirring at 0° C. for a further 6 hours
  2. customthe reaction was quenched by the addition of H2SO4 (35 mL, 5M)
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. filtrationfiltered through Celite®
  5. washThe filtrate was washed with 1M NaOH, water and brine
  6. customthe organic phase was isolated
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a4be47c0a0f041688663526d25a876cf
Source dataset
uspto-grants-2012_10
Patent number
US08288408B2

Reaction notes

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