Hydrochloric Acid → 2-{2-[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-amino]-ethyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 905856Notes

Reaction equation

HRID 905856 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][C:13](=O)[NH:14][CH2:15][C:16]1([OH:23])[CH2:21][CH2:20][N:19]([CH3:22])[CH2:18][CH2:17]1)=[O:5])[CH3:2].Cl.[OH-].[Na+]>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[CH:9][NH:8][C:7]=1[CH2:12][CH2:13][NH:14][CH2:15][C:16]1([OH:23])[CH2:17][CH2:18][N:19]([CH3:22])[CH2:20][CH2:21]1)=[O:5])[CH3:2]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 666092272-{[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-carbamoyl]-methyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 666078142-{2-[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-amino]-ethyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl esterYield 104.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

A stirred solution of 2-{[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-carbamoyl]-methyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (5.937 g, 17.62 mmol) in tetrahydrofuran (50 ml) was added slowly with another portion of 1M borane-tetrahydrofuran complex in tetrahydrofuran (52.1 ml, 52.1 mmol) under an argon atmosphere. Upon completion of the addition, the mixture was stirred for 1.5 hours at room temperature, heated to reflux for 1.5 hours and stirred at room temperature overnight. The resulting mixture was added with 1M borane-tetrahydrofuran complex in tetrahydrofuran (36 ml, 36 mmol) and stirred at room temperature for 0.5 hour, heated to reflux for another 5 hours. The mixture was added dropwise with 2 N hydrochloric acid in an ice-water bath. The resulting mixture was adjusted to pH 8 with 2N aqueous sodium hydroxide solution and distilled under reduced pressure. The residue was extracted with ethyl acetate (80 ml×8). The combined extracts were dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-{2-[(4-hydroxy-1-methyl-piperidin-4-ylmethyl)-amino]-ethyl}-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester (5.931 g) as an orange solid which was used as such.

Workup

  1. additionUpon completion of the addition
  2. temperatureheated
  3. temperatureto reflux for 1.5 hours
  4. stirringstirred at room temperature overnight
  5. stirringstirred at room temperature for 0.5 hour
  6. temperatureheated
  7. temperatureto reflux for another 5 hours
  8. distillationdistilled under reduced pressure
  9. extractionThe residue was extracted with ethyl acetate (80 ml×8)
  10. dry with materialThe combined extracts were dried with anhydrous sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-36b0dbf82650426baf5636660798ceb9
Source dataset
uspto-grants-2011_09
Patent number
US08012966B2

Reaction notes

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