Lithium Hydroxide → 6-Chloro-4-(isopropylamino)nicotinic acid

HRID 877526Notes

Reaction equation

HRID 877526 reaction equation
[Cl:1][C:2]1[CH:12]=[C:11]([NH:13][CH:14]2[CH2:17]C[CH2:15]2)[C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][N:3]=1.[Li+].[OH-]>C(O)C.O>[Cl:1][C:2]1[CH:12]=[C:11]([NH:13][CH:14]([CH3:17])[CH3:15])[C:5]([C:6]([OH:8])=[O:7])=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 89689654Ethyl 6-chloro-4-(cyclobutylamino)nicotinate

Product 1

HCID 896898576-Chloro-4-(isopropylamino)nicotinic acid

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

Ethyl 6-chloro-4-(cyclobutylamino)nicotinate (2) (3 g, 12.3 mmol) in ethanol (20 mL) and water (10 mL) was stirred at rt. LiOH (61.7 mmol, 5 equiv.) was added and the reaction mixture was stirred at room temperature for 4 h. The solvent was concentrated under reduced pressure. Diluted with EtOAc and added water. The aqueous layer was collected and acidified to pH 3-4 using solid citric acid. Solid material precipitated out. Filtered the solid material and dried under vacuum to furnish the title compound (3). 1H NMR: 400 MHz, DMSO-d6: δ1.20 (d, J=6.40 Hz, 6H), 3.80-3.88 (m, 1H), 6.80 (s, 1H), 8.20 (d, J=7.60 Hz, 1H), 8.51 (s, 1H), 13.33 (bs, 1H).

Workup

  1. concentrationThe solvent was concentrated under reduced pressure
  2. additionDiluted with EtOAc
  3. additionadded water
  4. customThe aqueous layer was collected
  5. customSolid material precipitated out
  6. filtrationFiltered the solid material
  7. customdried under vacuum

Sources & evidence

ORD record
ord-365eed2a25364686b300c7771c459fb2
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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