(R)-2-[(2-hydroxy-3-morpholin-4-yl-propylcarbamoyl)-methyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester → (R)-2-[2-(2-hydroxy-3-morpholin-4-yl-propylamino)-ethyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 2068725Notes

Reaction equation

HRID 2068725 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@@H:16]([OH:24])[CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:5])[CH3:2]>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@@H:16]([OH:24])[CH2:17][N:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1)=[O:5])[CH3:2]

Participants

3

Reactant 1

HCID 59375995(R)-2-[(2-hydroxy-3-morpholin-4-yl-propylcarbamoyl)-methyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 59375993(R)-2-[2-(2-hydroxy-3-morpholin-4-yl-propylamino)-ethyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl esterYield 93.75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(R)-2-[(2-hydroxy-3-morpholin-4-yl-propylcarbamoyl)-methyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 5c (2.332 g, 6.6 mmol) was dissolved in 23 mL of anhydrous tetrahydrofuran under an argon atmosphere, and borane-tertrahydrofuran complex in tetrahydrofuran (23.12 mL, 1 mol/L, 23.12 mmol) was then added dropwise to the solution in an ice-water bath. Upon completion of the addition, the ice-water bath was removed. The reaction system was allowed to warm up to room temperature and refluxed at 95° C. in an oil bath for 1 hour. The reaction was completed until TLC showed the disappearance of starting materials. The solvent was evaporated under reduced pressure, and 5 mL of hydrochloric acid (2N) was then added to the residue. The mixture was stirred for 0.5 hour, and 5 mL of iced water was then added to the mixture. The mixture was adjusted to pH about 10 with 10N sodium hydroxide solution. The mixture was extracted with ethyl acetate (100 mL×2). The combined organic extracts were washed with saturated brine (50 mL), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to give the title compound (R)-2-[2-(2-hydroxy-3-morpholin-4-yl-propylamino)-ethyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 5d (2.1 g, yield 93.75%) as a white solid.

Workup

  1. additionUpon completion of the addition
  2. customthe ice-water bath was removed
  3. temperaturerefluxed at 95° C. in an oil bath for 1 hour
  4. customThe solvent was evaporated under reduced pressure, and 5 mL of hydrochloric acid (2N)
  5. additionwas then added to the residue
  6. addition5 mL of iced water was then added to the mixture
  7. extractionThe mixture was extracted with ethyl acetate (100 mL×2)
  8. washThe combined organic extracts were washed with saturated brine (50 mL)
  9. dry with materialdried over anhydrous magnesium sulfate
  10. filtrationfiltered
  11. customto remove the drying agent
  12. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-563ac0cf70e4431387f18b112674636a
Source dataset
uspto-grants-2012_10
Patent number
US08299069B2

Reaction notes

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