Water → 2-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-6-chloro-4-pyridinecarbonitrile

HRID 1874921Notes

Reaction equation

HRID 1874921 reaction equation
[N:1]([CH2:4][C:5]1[C:6]([F:22])=[C:7]([O:12][C:13]2[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([Cl:21])[N:14]=2)[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:22])=[C:7]([O:12][C:13]2[CH:18]=[C:17]([C:19]#[N:20])[CH:16]=[C:15]([Cl:21])[N:14]=2)[C:8]([Cl:11])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 962WaterHCID 11776TriphenylphosphineHCID 866448962-{[3-(Azidomethyl)-6-chloro-2-fluorophenyl]oxy}-6-chloro-4-pyridinecarbonitrile

Product 1

HCID 866448972-{[3-(Aminomethyl)-6-chloro-2-fluorophenyl]oxy}-6-chloro-4-pyridinecarbonitrileYield 43.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

2-{[3-(azidomethyl)-6-chloro-2-fluorophenyl]oxy}-6-chloro-4-pyridinecarbonitrile (0.402 g, 1.189 mmol) dissolved in THF (10 mL) was treated successively with triphenylphosphine (0.468 g, 1.783 mmol) and water (0.107 mL, 5.94 mmol) at 25° C. for 16 h with stirring. The reaction mixture was concentrated to dryness and purified on 40 g silica gel eluted successively with EtOAc (to remove tripheylphosphine oxide) followed by 0 to 10% CH3OH/DCM to give 2-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-6-chloro-4-pyridinecarbonitrile (0.161 g, 0.516 mmol, 43.4% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.96 (s, 1H), 7.93 (s, 1H), 7.44-7.55 (m, 2H), 3.77 (s, 2H), 1.94 (br. s., 2H). LC-MS (ES+) m/z 312.29, 314.28 [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 tripheylphosphine oxide)

Sources & evidence

ORD record
ord-18db296c63ae4649913bd8fa9159095f
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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