Acetic Acid → 3-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl]amino]benzonitrile

HRID 990518Notes

Reaction equation

HRID 990518 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[F:10][C:11]([F:24])([O:15][C:16]1[CH:17]=[C:18]([CH:21]=[CH:22][CH:23]=1)[CH:19]=O)[CH:12]([F:14])[F:13].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>ClC(Cl)C>[F:10][C:11]([F:24])([O:15][C:16]1[CH:17]=[C:18]([CH2:19][NH:1][C:2]2[CH:3]=[C:4]([CH:7]=[CH:8][CH:9]=2)[C:5]#[N:6])[CH:21]=[CH:22][CH:23]=1)[CH:12]([F:13])[F:14]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 167023-AminobenzonitrileHCID 118803Benzaldehyde, 3-(1,1,2,2-tetrafluoroethoxy)-HCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 235060273-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl]amino]benzonitrileYield 54.1%

Reagents, catalysts & solvents 1

HCID 63651,1-DichloroethaneSolvent

Procedure

A solution of 3-aminobenzonitrile (1.06 g, 9.1 mmol) and 3-(1,1,2,2-tetrafluoroethoxy)benzaldehyde (2.00g, 9.01 mmol) was dissolved in 25 mL of dichloroethane and acetic acid (536 mL, 9.37 mmol), then solid NaBH(OAc)3 (2.48 g, 11.7 mmol) was added. The mixture was stirred at room temperature for 3 hours, then quenched with water and extracted with dichloromethane. The organic layer was washed with saturated NaHCO3, then dried over MgSO4, and evaporated. The crude product was purified by MPLC on silica gel eluting with 20% to 30% ethyl acetate in hexane to give 1.58 g (54%) of the desired 3-[[[3-(1,1,2,2-tetrafluoroethoxy)-phenyl]methyl]amino]benzonitrile product as a clear oil. 1H NMR (CDCl3) δ4.38 (s, 3H), 5.89 (dt, 1H), 6.79 (t, 1H), 6.98 (d, 2H), 7.12-7.28 (m, 4H), 7.40 (t, 1H).

Workup

  1. customquenched with water
  2. extractionextracted with dichloromethane
  3. washThe organic layer was washed with saturated NaHCO3
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe crude product was purified by MPLC on silica gel eluting with 20% to 30% ethyl acetate in hexane

Sources & evidence

ORD record
ord-d38434e7ba5f4ca6b6501573ea87213f
Source dataset
uspto-grants-2002_10
Patent number
US06458852B1

Reaction notes

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