Lithium borohydride → 4-[(2-Hydroxyethyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrile

HRID 1173404Notes

Reaction equation

HRID 1173404 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:15][C:16]([F:19])([F:18])[F:17])[CH2:10][C:11](OC)=[O:12])=[CH:5][C:4]=1[C:20]([F:23])([F:22])[F:21])#[N:2].[Li+].[BH4-]>C1COCC1>[OH:12][CH2:11][CH2:10][N:9]([CH2:15][C:16]([F:17])([F:18])[F:19])[C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[C:4]([C:20]([F:22])([F:23])[F:21])[CH:5]=1

Participants

4

Reactant 2

HCID 4148881Lithium borohydrideHCID 11439223Methyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycinate

Product 1

HCID 866237314-[(2-Hydroxyethyl)(2,2,2-trifluoroethyl)amino]-2-(trifluoromethyl)benzonitrileYield 79.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl N-[4-cyano-3-(trifluoromethyl)phenyl]-N-(2,2,2-trifluoroethyl)glycinate (1.67 g, 4.91 mmol) in THF (17 mL) at 0° C. was added a solution of LiBH4 in THF (4.91 mL of a 2 M solution, 9.82 mmol), dropwise over 5 min. The cooling bath was removed, and the mixture was stirred 19 h at rt. The mixture was cooled to 0° C., quenched by dropwise addition of sat'd NH4Cl and poured into water. The whole was extracted with EtOAc (×3). Combined organic portions were washed (water, brine), dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording 1.22 g of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ 7.64 (d, J=9.1 Hz, 1H), 7.10 (d, J=2.7 Hz, 1H), 6.96 (dd, J=8.8, 2.5 Hz, 1H), 4.16 (q, J=8.5 Hz, 2H), 3.95 (app. q, J=5.1 Hz, 2H), 3.76 (t, J=5.4 Hz, 2H), 1.68 (t, J=4.6 Hz, 1H); MS (APCI) m/z 313 (M+1).

Workup

  1. customThe cooling bath was removed
  2. temperatureThe mixture was cooled to 0° C.
  3. customquenched by dropwise addition of sat'd NH4Cl
  4. additionpoured into water
  5. extractionThe whole was extracted with EtOAc (×3)
  6. washCombined organic portions were washed (water, brine)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-2e130c95ab904bf48d04a6e1f44c829b
Source dataset
uspto-grants-2010_11
Patent number
US07834063B2

Reaction notes

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