Sodium borohydride → 3-chloro-4-[(2,4-difluorobenzyl)oxy]-1-{[5-(hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(1H)-one

HRID 1867043Notes

Reaction equation

HRID 1867043 reaction equation
[Cl:1][C:2]1[C:3](=[O:31])[N:4]([CH2:19][C:20]2[N:21]=[CH:22][C:23]([C:26](OCC)=[O:27])=[N:24][CH:25]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17].[BH4-].[Na+]>C1COCC1.C(O)(C)(C)C>[Cl:1][C:2]1[C:3](=[O:31])[N:4]([CH2:19][C:20]2[CH:25]=[N:24][C:23]([CH2:26][OH:27])=[CH:22][N:21]=2)[C:5]([CH3:18])=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][C:11]=1[F:17]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 22050532Ethyl 5-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl-2-oxopyridin-1(2H)-yl]methyl}pyrazine-2-carboxylate

Product 1

HCID 220499683-chloro-4-[(2,4-difluorobenzyl)oxy]-1-{[5-(hydroxymethyl)pyrazin-2-yl]methyl}-6-methylpyridin-2(1H)-oneYield 44%

Reagents, catalysts & solvents 1

HCID 66775918Tert-butanol tetrahydrofuranSolvent

Procedure

To a suspension of ethyl 5-{[3-chloro-4-[(2,4-difluorobenzyl)oxy]-6-methyl 2-oxopyridin-1(2H)-yl]methyl}pyrazine-2-carboxylate (4.0 g, 8.9 mmol) in THF:t-butanol (1:1) (10 mL) was added NaBH4 (0.46 g, 12.4 mmol). The reaction stirred at room temperature under argon overnight. The reaction mixture was quenched with acetic acid (2 mL) and the solvent was removed in vacuo. The residue was triturated with water and filtered. The solid was washed with fresh water followed by ethanol. The solid was purified by flash column chromatography (100% ethyl acetate). The appropriate fractions were combined and concentrated under reduced pressure to afford the desired compound (1.58 g, 44%) as a white solid. 1H NMR (CD3OD, 400 MHz) δ 8.59 (s, 1H), 8.56 (s, 1H), 7.52 (m, 1H), 7.01 (m, 2H), 6.55 (m, 1H), 5.45 (s, 2H), 5.29 (s, 2H), 4.71 (2H), 2.54 (s, 3H); ES-HRMS m/z 408.0940 (M+H calculated for C19H17N3O3ClF2 requires 408.0921).

Workup

  1. customThe reaction mixture was quenched with acetic acid (2 mL)
  2. customthe solvent was removed in vacuo
  3. customThe residue was triturated with water
  4. filtrationfiltered
  5. washThe solid was washed with fresh water
  6. customThe solid was purified by flash column chromatography (100% ethyl acetate)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-71770cd6d97b46759064116617a19320
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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