Acetic Acid → HCID 962168, compound

HRID 2394267Notes

Reaction equation

HRID 2394267 reaction equation
[CH:1](=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:9][C:10]1[CH:11]=[C:12]([CH:14]=[C:15]([Cl:17])[CH:16]=1)[NH2:13].CC(O)=O.[BH3-]C#N.[Na+]>CO>[CH2:1]([NH:13][C:12]1[CH:11]=[C:10]([Cl:9])[CH:16]=[C:15]([Cl:17])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 240BenzaldehydeHCID 122813,5-DichloroanilineHCID 5003444Sodium cyanoborohydride

Product 1

HCID 962168HCID 962168, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of benzaldehyde (1.04 g, 9.40 mmol), 3,5-dichloroaniline (1.71 g, 10.60 mmol), and HOAc (0.20 mL) in MeOH (35 mL) was cooled to 0° C. Then a solution of NaBH3CN (28.0 mL, 28.0 mmol, 1.0 M solution in THF) was added dropwise via a syringe pump over 0.25 h. The solution was allowed to stir an additional 0.3 h at 0° C., and then room temperature for 18 h. The excess NaBH3CN was quenched with HCl and the solvent was removed under reduced pressure. The resulting oil was dissolved in EtOAc/H2O, basified with NaOH, and extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. The resulting oil was purified by chromatography (SiO2, 15:1 hexanes/EtOAc) to provide N-benzyl-3,5-dichloroaniline as a white solid. This compound was coupled to 2-chloro-4-trifluoromethylpyrimidine-5-carbonyl chloride as described and purified by chromatography (SiO2, 9:1 hexanes/EtOAc) to provide the title compound (15% yield) as a white foam; m.p. 102°-104° C.

Workup

  1. waitroom temperature for 18 h
  2. customThe excess NaBH3CN was quenched with HCl
  3. customthe solvent was removed under reduced pressure
  4. dissolutionThe resulting oil was dissolved in EtOAc/H2O
  5. extractionextracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customthe solvent removed under reduced pressure
  10. customThe resulting oil was purified by chromatography (SiO2, 15:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-85e66fb94f494b538a8da48f76e7cf2d
Source dataset
uspto-grants-1998_09
Patent number
US05811428

Reaction notes

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