Potassium sodium tartarate → (1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamine

HRID 878460Notes

Reaction equation

HRID 878460 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([C:11]#[N:12])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+]>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([Cl:13])[C:5]([C:8]2([CH2:11][NH2:12])[CH2:9][CH2:10]2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 9855836Potassium sodium tartarateHCID 21225700Diisobutylaluminumhydride2×HCID 715592791-(5-Bromo-3-chloropyridin-2-yl)cyclopropane-1-carbonitrile

Product 1

HCID 89544163(1-(5-Bromo-3-chloropyridin-2-yl)cyclopropyl)methanamineYield 46.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

106 mg of 1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropanecarbonitrile (step 2) was dissolved in 2 ml of dichloromethane and was cooled down to −78° C. Then 0.91 ml of diisobutylaluminium hydride (1 M in tetrahydrofuran) was added dropwise. The reaction mixture was stirred at −78° C. for 1h, then at ambient temperature for three days. Then 0.40 ml of diisobutylaluminium hydride solution was added again at −78° C. and the reaction mixture was warmed to 40° C. and stirred for 24 hours. The reaction mixture was poured into a saturated solution of potassium sodium tartrate and the resulting mixture was stirred for 1 hour. The aqueous phase was extracted with three 25 ml portions dichloromethane. The organic phase was dried over sodium sulfate, filtered and concentrated. 140 mg of crude material was obtained as a yellow sticky solid. The residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate. The aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide and extracted with ethyl acetate. The organic phase was dried over sodium sulfate, filtered and concentrated. Thus, 50 mg of C-[1-(5-bromo-3-chloro-pyridin-2-yl)-cyclopropyl]-methylamine was obtained as a yellow sticky solid. 1H-NMR (CDCl3): 8.50 ppm (s, 1H), 7.83 ppm (s, 1H), 2.95 ppm (s, 2H), 1.40 ppm (s, 2H, broad), 0.99 ppm (m, 2H), 0.90 ppm (m, 2H).

Workup

  1. temperaturethe reaction mixture was warmed to 40° C.
  2. stirringthe resulting mixture was stirred for 1 hour
  3. extractionThe aqueous phase was extracted with three 25 ml portions dichloromethane
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. custom140 mg of crude material was obtained as a yellow sticky solid
  8. customThe residue was partitioned between 1N aqueous hydrochloric acid and ethyl acetate
  9. additionThe aqueous phase was adjusted to pH 14 by addition of an aqueous solution of sodium hydroxide
  10. extractionextracted with ethyl acetate
  11. dry with materialThe organic phase was dried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-6e7af893ad554bb6bb1d09a10fef6c67
Source dataset
uspto-grants-2015_03
Patent number
US08987465B2

Reaction notes

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