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Sodium borohydride → 6-Aminomethyl-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

HRID 1500694
Notes
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Reaction equation

HRID 1500694 reaction equation
[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([C:11]#[N:12])=[N:6][C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([Si:20]([CH3:23])([CH3:22])[CH3:21])=[CH:16][C:15]=1[F:24].[BH4-].[Na+]>CO.[Co](Cl)Cl>[CH3:1][O:2][C:3](=[O:25])[C:4]1[CH:9]=[C:8]([F:10])[C:7]([CH2:11][NH2:12])=[N:6][C:5]=1[NH:13][C:14]1[CH:19]=[CH:18][C:17]([Si:20]([CH3:22])([CH3:21])[CH3:23])=[CH:16][C:15]=1[F:24]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 591401176-Cyano-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester

Product 1

HCID 591401506-Aminomethyl-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl esterYield 34.6%

Reagents, catalysts & solvents 2

HCID 24288Cobalt(II) chlorideCatalyst
HCID 887
Methanol
Solvent

Conditions

Temperature
0 °C

Procedure

To a suspension of 6-cyano-5-fluoro-2-(2-fluoro-4-trimethylsilanyl-phenylamino)-nicotinic acid methyl ester (5.7 g, 15.8 mmol) in methanol (130 mL) was added cobalt (II) chloride (7.5 g, 31.6 mmol). The reaction mixture was stirred for 10 minutes, then cooled to 0° C. and sodium borohydride (6.0 g, 158 mmol) was added in small portions over 30 minutes. The reaction mixture was stirred at 0° C. for 15 minutes and then at room temperature for 1 hour. The reaction was quenched by addition of concentrated hydrochloric acid (20 mL) and the mixture stirred for 15 minutes. The reaction mixture was filtered to remove a white solid, which was washed with dichloromethane, and the filtrate was concentrated under reduced pressure. The resultant residue was dissolved in ethyl acetate and washed with a saturated solution of sodium bicarbonate, 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 (2.0 g, 34%). LCMS (method B): RT=2.77 min, [M+H]+=366.

Workup

  1. stirringThe reaction mixture was stirred at 0° C. for 15 minutes
  2. waitat room temperature for 1 hour
  3. customThe reaction was quenched by addition of concentrated hydrochloric acid (20 mL)
  4. stirringthe mixture stirred for 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 under reduced pressure
  9. dissolutionThe resultant residue was dissolved in ethyl acetate
  10. washwashed with a saturated solution of sodium bicarbonate
  11. customThe organic phase was isolated
  12. dry with materialdried (Na2SO4)
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-18c0f874881a451ca93cabb8f55517db
Source dataset
uspto-grants-2015_12
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09206174B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes