Potassium Carbonate → 2-Chloro-3-(propan-2-yl)pyridine

HRID 1484017Notes

Reaction equation

HRID 1484017 reaction equation
N[C:2]1[C:3]([Cl:8])=[N:4][CH:5]=[CH:6][CH:7]=1.[BH-](O[C:19]([CH3:21])=O)(OC(C)=O)OC(C)=O.[Na+].[C:23](=O)([O-])[O-].[K+].[K+]>ClCCCl.O.CO.CC(O)=O.CC(C)=O>[Cl:8][C:3]1[C:2]([CH:19]([CH3:21])[CH3:23])=[CH:7][CH:6]=[CH:5][N:4]=1

Participants

9

Reactant 3

HCID 11430Potassium CarbonateHCID 805282-Chloro-3-pyridylamineHCID 5049666Sodium triacetoxyborohydride2×

Product 1

HCID 234369862-Chloro-3-(propan-2-yl)pyridine

Reagents, catalysts & solvents 5

HCID 111,2-DichloroethaneSolvent2×HCID 176Acetic AcidSolvent2×HCID 180AcetoneSolvent2×HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Acetone (1.1 mL, 14.89 mmol) was added to a stirred solution of 3-amino-2-chloropyridine 1 (1.662 g, 12.67 mmol) in 1,2-dichloroethane at room temperature. And then acetic acid (0.7 mL, 12.22 mmol) was added. After about 10 min, NaB(OAc)3H (3.005 g, 13.47 mmol) was added. The resulting mixture was stirred at room temperature for 24 h. More of acetone (5.5 ml) and NaB(OAc)3H (356 mg) and DCE (5 mL) were added. HOAc (0.35 mL) was added. After 2 h, MeOH (5 mL) was added. After overnight at room temperature, water was added to quench the reaction. Sat. aqueous potassium carbonate was added to neutralize the acid. The organic phase was separated and the aqueous was extracted with dichloromethane (2×20 mL). The combined organic solution was washed with brine, dried over Na2SO4, concentrated. The residue was separated by flash column chromatography on silica gel, eluting with 5-30% EtOAc/hexane to afford 1.20 g product as colorless oil, as well as 0.6326 g of starting material. 1H-NMR (CDCl3): 7.669 (dd, J=4.5-5.0 Hz and 1.5 Hz, 1H, Ar—H), 7.075 (dd, J=8.0 Hz and 4.5-5.0 Hz, 1H, Ar—H), 6.875 (dd, J=8.0 Hz and 1.5 Hz, 1H, Ar—H), 4.194 (br, 1H, NH) 3.644-3.578 (m, 1H, CH), 1.260 (d, J=6.5 Hz, 6H, 2 CH3). LC-MS: 171.1 (MH+).

Workup

  1. waitAfter 2 h
  2. waitAfter overnight at room temperature
  3. customto quench
  4. customthe reaction
  5. customThe organic phase was separated
  6. extractionthe aqueous was extracted with dichloromethane (2×20 mL)
  7. washThe combined organic solution was washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe residue was separated by flash column chromatography on silica gel
  11. washeluting with 5-30% EtOAc/hexane

Sources & evidence

ORD record
ord-649c2d04d7ed4d609a974087d0ce945f
Source dataset
uspto-grants-2016_08
Patent number
US09421204B2

Reaction notes

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