Triphenylphosphine → 2-(5-Chloropyridin-2-yl)-2,2-difluoroethan-1-amine

HRID 1987071Notes

Reaction equation

HRID 1987071 reaction equation
[N:1]([CH2:4][C:5]([C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][N:9]=1)([F:7])[F:6])=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH-].[NH4+].[OH-].[Na+]>C1COCC1>[F:7][C:5]([F:6])([C:8]1[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][N:9]=1)[CH2:4][NH2:1]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 14923Ammonium HydroxideHCID 86006460HCID 86006460, compound

Product 1

HCID 534408412-(5-Chloropyridin-2-yl)-2,2-difluoroethan-1-amineYield 93.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 2-(2-Azido-1,1-difluoro-ethyl)-5-chloro-pyridine (1.94 g, 8.87 mmol) (prepared essentially as described for Example 14b) in THF (30 mL) cooled in an ice bath were added triphenylphosphine pellets (2.6 g, 9.76 mmol). The mixture was stirred at room temperature for 16 h. Ammonium hydroxide solution (10 mL) was added to the mixture followed by additional stirring for 4 h. NaOH solution (3 N, 40 mL) was then added and the mixture was heated at 40° C. for 1 h. The organic layer was separated and washed with HCl solution (2 N, 60 mL). The aqueous layer was then basified with 4 N NaOH solution and extracted with EtOAc twice. The solvent was evaporated to leave a pale yellow oil (1.6 g, 93% yield). 1H NMR (300 Hz, CDCl3) δ 8.59 (d, 1H), 7.78 (dd, 1H), 7.62 (d, 1H), 3.40 (t, 2H); LC/MS (m/z) [M+1]+ 193.0 (calculated for C7H7ClF2N2, 192.0).

Workup

  1. temperaturecooled in an ice bath
  2. stirringby additional stirring for 4 h
  3. temperaturethe mixture was heated at 40° C. for 1 h
  4. customThe organic layer was separated
  5. washwashed with HCl solution (2 N, 60 mL)
  6. extractionextracted with EtOAc twice
  7. customThe solvent was evaporated

Sources & evidence

ORD record
ord-62fcd205c3684cdfb7ff75622e628822
Source dataset
uspto-grants-2009_06
Patent number
US07550474B2

Reaction notes

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