Hydrochloric Acid → HCID 86618563, compound

HRID 913160Notes

Reaction equation

HRID 913160 reaction equation
C[O:2][C:3](=[O:32])[C:4]1[CH:9]=[C:8]([NH:10][CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH2:25][CH3:26])[C:21]([Cl:27])=[C:20]([O:28][CH2:29][CH3:30])[CH:19]=3)[CH2:13][CH2:12]2)[N:7]=[C:6]([Cl:31])[CH:5]=1.[Li+].[OH-].O.Cl>C1COCC1.CO>[Cl:31][C:6]1[CH:5]=[C:4]([CH:9]=[C:8]([NH:10][CH:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]3[CH:23]=[C:22]([O:24][CH2:25][CH3:26])[C:21]([Cl:27])=[C:20]([O:28][CH2:29][CH3:30])[CH:19]=3)[CH2:13][CH2:12]2)[N:7]=1)[C:3]([OH:32])=[O:2]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 3939Lithium HydroxideHCID 86618564HCID 86618564, compound

Product 1

HCID 86618563HCID 86618563, compoundYield 73.2%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a stirred solution of 2-chloro-6-[1-(4-chloro-3,5-diethoxy-benzyl)-piperidin-4-ylamino]-isonicotinic acid methyl ester (0.17 g, 0.35 mmol, 1.0 equiv; example 224) in THF/methanol (2:1) (15 mL) was added a solution of 1 M LiOH (0.87 mL, 0.87 mmol. 2.5 equiv) drop by drop. After 16 h, the reaction mixture was poured into ice water, the pH of the water phase adjusted to 3-4 with diluted HCl and the mixture extracted twice with dichloromethane. The organic phases were washed with water, dried over MgSO4, filtered and concentrated by evaporation under reduced pressure. The crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol to give 0.12 g (73%) of the title compound as colorless solid. MS (ISP): 468.3 [M+H]+.

Workup

  1. extractionthe mixture extracted twice with dichloromethane
  2. washThe organic phases were washed with water
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated by evaporation under reduced pressure
  6. customThe crude product was purified by column chromatography on silica eluting with a gradient of dichloromethane/methanol

Sources & evidence

ORD record
ord-a81e489934164c8a9a650f5299bad0d2
Source dataset
uspto-grants-2011_09
Patent number
US08026255B2

Reaction notes

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