Methanol → 2-Chloro-4-fluorobenzylamine

HRID 2251974Notes

Reaction equation

HRID 2251974 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:20]([CH2:23][C:24]1[CH:29]=[CH:28][C:27]([F:30])=[CH:26][C:25]=1[Cl:31])=[N+]=[N-].N#N.CO>C1COCC1.O>[Cl:31][C:25]1[CH:26]=[C:27]([F:30])[CH:28]=[CH:29][C:24]=1[CH2:23][NH2:20]

Participants

7

Reactant 4

HCID 887MethanolHCID 947NitrogenHCID 11776TriphenylphosphineHCID 433071181-(Azidomethyl)-2-chloro-4-fluorobenzene

Product 1

HCID 1399092-Chloro-4-fluorobenzylamineYield 73.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Add triphenylphosphine (129.9 g, 495 mmol) to a solution of 1-azidomethyl-2-chloro-4-fluoro-benzene (61.2 g, 330 mmol) in THF (500 mL) and water (30 mL). Stir at RT until no more N2 is evolved. Add 100 mL MeOH and stir at RT overnight. Concentrate; acidify to pH 1 with 1N HCl solution, wash with CH2Cl2 (3 times). Basify aqueous layer with 5N NaOH solution, extract with CH2Cl2 (3 times), dry over MgSO4. Concentrate to afford the title compound (38.5 g, 73%) as a clear liquid. MS(IS) 160 (M+1). 1H NMR (400 MHz, CDCl3): 3.90 (s, 2H); 6.96 (t, 1H, J=6.4 Hz); 7.11 (d, 1H, J=8.3 Hz); 7.36 (t, 1H, J=6.4 Hz).

Workup

  1. concentrationConcentrate
  2. washwash with CH2Cl2 (3 times)
  3. extractionBasify aqueous layer with 5N NaOH solution, extract with CH2Cl2 (3 times)
  4. dry with materialdry over MgSO4
  5. concentrationConcentrate

Sources & evidence

ORD record
ord-4f32b2125cfb42eda21981a8d2c5bbc9
Source dataset
uspto-grants-2008_01
Patent number
US07320994B2

Reaction notes

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