Water → 3-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-2,5-dichlorobenzonitrile

HRID 1874896Notes

Reaction equation

HRID 1874896 reaction equation
[N:1]([CH2:4][C:5]1[C:6]([F:23])=[C:7]([O:12][C:13]2[C:14]([Cl:22])=[C:15]([CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:16]#[N:17])[C:8]([Cl:11])=[CH:9][CH:10]=1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>C1COCC1>[NH2:1][CH2:4][C:5]1[C:6]([F:23])=[C:7]([O:12][C:13]2[C:14]([Cl:22])=[C:15]([CH:18]=[C:19]([Cl:21])[CH:20]=2)[C:16]#[N:17])[C:8]([Cl:11])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 11776TriphenylphosphineHCID 866448913-{[3-(Azidomethyl)-6-chloro-2-fluorophenyl]oxy}-2,5-dichlorobenzonitrile

Product 1

HCID 684876593-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-2,5-dichlorobenzonitrileYield 93%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

3-{[3-(azidomethyl)-6-chloro-2-fluorophenyl]oxy}-2,5-dichlorobenzonitrile (0.565 g, 1.521 mmol) was dissolved in THF (5 mL) and was treated successively with triphenylphosphine (0.598 g, 2.281 mmol) and water (0.137 g, 7.60 mmol) at 25° C. for 3 days with stirring. The reaction mixture was concentrated to dryness and purified on 40 g silica gel eluted successively with EtOAc (to remove triphylphosphine oxide) followed by a gradient of 100% EtOAc to 10% CH3OH/DCM to give the desired product, 3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-2,5-dichlorobenzonitrile (0.487 g, 1.409 mmol, 93% yield), as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.00 (d, J=2.20 Hz, 1H), 7.48-7.58 (m, 2H), 7.19 (d, J=1.83 Hz, 1H), 3.77 (s, 2H), 1.94 (br. s., 2H). LC-MS (ES+) m/z 344.89, 346.89, 348.89 [M+H].

Workup

  1. concentrationThe reaction mixture was concentrated to dryness
  2. custompurified on 40 g silica gel
  3. washeluted successively with EtOAc (to remove triphylphosphine oxide)

Sources & evidence

ORD record
ord-553641baad7240db83341132f8e3f1df
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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