Sodium borohydride → 6-Aminomethyl-2-(2-fluoro-4-trimethylsilanyl-phenylamino)nicotinic acid methyl ester

HRID 2076153Notes

Reaction equation

HRID 2076153 reaction equation
[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([C:10]#[N:11])=[N:6][C:5]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Si:19]([CH3:22])([CH3:21])[CH3:20])=[CH:15][C:14]=1[F:23].[BH4-].[Na+]>CO.[Co](Cl)Cl>[CH3:1][O:2][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([CH2:10][NH2:11])=[N:6][C:5]=1[NH:12][C:13]1[CH:18]=[CH:17][C:16]([Si:19]([CH3:21])([CH3:20])[CH3:22])=[CH:15][C:14]=1[F:23]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 591401856-Cyano-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

Product 1

HCID 591401646-Aminomethyl-2-(2-fluoro-4-trimethylsilanyl-phenylamino)nicotinic acid methyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 24288Cobalt(II) chlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 6-cyano-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (13.1 g, 38.2 mmol) in methanol (285 mL) was added cobalt (II) chloride (18.2 g, 76.4 mmol). The reaction mixture was cooled to 0° C. and sodium borohydride (14.5 g, 382 mmol) was added in small portions over 20 minutes (CAUTION: EFFERVESCENCE). The reaction mixture was stirred at 0° C. for 1 hour. The reaction was quenched by the addition of concentrated hydrochloric acid (50 mL) and the mixture stirred at 0° C. for 10 minutes and at room temperature for 45 minutes. Diethylenetriamine (9 mL) was then added and the mixture stirred for a further 15 minutes. The reaction mixture was filtered to remove a white solid, which was washed with dichloromethane. The filtrate was concentrated in vacuo and the resultant residue was dissolved in ethyl acetate and washed with a saturated solution of sodium hydrogen carbonate, followed by water then brine. The organic phase was isolated, dried (Na2SO4), filtered and concentrated in vacuo to afford the title compound as a brown solid (13.2 g, 100%). LCMS (method B): RT=2.82 min, M+H+=348.

Workup

  1. customThe reaction was quenched by the addition of concentrated hydrochloric acid (50 mL)
  2. stirringthe mixture stirred at 0° C. for 10 minutes and at room temperature for 45 minutes
  3. additionDiethylenetriamine (9 mL) was then added
  4. stirringthe mixture stirred for a further 15 minutes
  5. filtrationThe reaction mixture was filtered
  6. customto remove a white solid, which
  7. washwas washed with dichloromethane
  8. concentrationThe filtrate was concentrated in vacuo
  9. dissolutionthe resultant residue was dissolved in ethyl acetate
  10. washwashed with a saturated solution of sodium hydrogen carbonate
  11. customThe organic phase was isolated
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3da407634a584ac78e75152ada3f2946
Source dataset
uspto-grants-2011_04
Patent number
US07923456B2

Reaction notes

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