Acetic Acid → 6-chloro-N-(propan-2-yl)pyridin-3-amine

HRID 914699Notes

Reaction equation

HRID 914699 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH2:8])=[CH:4][N:3]=1.[CH3:9][C:10]([CH3:12])=O.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].CC(O)=O>ClC(Cl)C.[OH-].[Na+]>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([NH:8][CH:10]([CH3:12])[CH3:9])=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 180AcetoneHCID 793055-Amino-2-chloropyridineHCID 5049666Sodium triacetoxyborohydride

Product 1

HCID 589579206-chloro-N-(propan-2-yl)pyridin-3-amineYield 76.3%

Reagents, catalysts & solvents 2

HCID 63651,1-DichloroethaneSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 2-chloro-5-aminopyridine (500 mg, 3.88 mmol) and acetone (250 μL, 4.27 mmol) in dichloroethane (13 mL) was added NaBH(OAc)3 (989 mg, 4.66 mmol) and AcOH (330 μL, 5.82 mmol). The reaction was stirred for 24 hours and was diluted with 1N NaOH. The aqueous solution was washed with CH2Cl2 (3×). The combined organic solutions were dried (Na2SO4), filtered and concentrated. Purification by medium pressure chromatography eluting with a solvent gradient (2% MeOH in CH2Cl2 to 5% MeOH in CH2Cl2) provided 505.2 mg of (6-chloro-pyridin-3-yl)-isopropyl-amine. 1H NMR (CD3OD) δ 7.64 (d, 1H), 7.10 (d, 1H), 6.99 (dd, 1H), 3.55 (m, 1H), 1.17 (d, 6H).

Workup

  1. washThe aqueous solution was washed with CH2Cl2 (3×)
  2. dry with materialThe combined organic solutions were dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customPurification by medium pressure chromatography
  6. washeluting with a solvent gradient (2% MeOH in CH2Cl2 to 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-ec3bcb59bf8c46119404ac53ab53e9d7
Source dataset
uspto-grants-2007_09
Patent number
US07265104B2

Reaction notes

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