Water → 4-chloro-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide

HRID 655769Notes

Reaction equation

HRID 655769 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][N:14](C(OCC)=O)[CH2:13][C@@H:12]2[O:22][CH2:23][CH3:24])=[O:9])[NH:5][C:6]=1[CH3:7].[OH-].[K+].O.NN.O>C(O)CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([NH:10][C@@H:11]2[CH2:16][CH2:15][NH:14][CH2:13][C@@H:12]2[O:22][CH2:23][CH3:24])=[O:9])[NH:5][C:6]=1[CH3:7]

Participants

6

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 24654Hydrazine hydrate (1:1)HCID 59402578Ethyl (3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate2×

Product 1

HCID 594025594-chloro-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamideYield 37.5%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Procedure

A solution of ethyl (3S,4R)-4-{[(4-chloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}-3-ethoxypiperidine-1-carboxylate (Intermediate 34, 1.6 g, 4.48 mmol), potassium hydroxide (1.76 g, 31.37 mmol), and hydrazine hydrate (1.6 mL, 31.37 mmol) in ethylene glycol (180 mL) was stirred for 40 h at 120° C. The reaction mixture was poured in to water (120 mL) and extracted with ethyl acetate (2×150 mL). The combined organic extracts were dried over anhydrous sodium sulphate, filtered, concentrated in vacuo to yield the crude product which was triturated with water (30 mL) to afford 4-chloro-N-[(3S,4R)-3-ethoxypiperidin-4-yl]-5-methyl-1H-pyrrole-2-carboxamide 480 mg (37%) as solid.

Workup

  1. extractionextracted with ethyl acetate (2×150 mL)
  2. dry with materialThe combined organic extracts were dried over anhydrous sodium sulphate
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customto yield the crude product which
  6. customwas triturated with water (30 mL)

Sources & evidence

ORD record
ord-69439298909d4390b9e750427ebc5318
Source dataset
uspto-grants-2011_12
Patent number
US08071605B2

Reaction notes

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