HCID 59375990, compound → HCID 59375985, compound

HRID 2068717Notes

Reaction equation

HRID 2068717 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 59375990HCID 59375990, compound

Product 1

HCID 59375985HCID 59375985, compoundYield 96%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(S)-2-[(2-Hydroxy-3-morpholin-4-yl-propylcarbamoyl)-methyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 1c (16.9 g, 47.9 mmol) was dissolved in 143.6 mL of anhydrous tetrahydrofuran under an argon atmosphere, and borane-tertrahydrofuran complex in tetrahydrofuran (143.6 mL, 1 mol/L, 143.6 mmol) was then added 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 and. The reaction was completed until TLC showed the disappearance of starting materials. The solvent was evaporated under reduced pressure, and 150 mL of hydrochloric acid (2N) was then added to the residue. The mixture was stirred for 0.5 hour, and 50 mL of iced water was then added. The mixture was adjusted to pH about 10 with 10N sodium hydroxide solution and extracted with ethyl acetate (200 mL ×2). The combined organic extracts were washed with saturated brine (100 mL), dried over anhydrous magnesium sulfate, filtered to remove the drying agent and concentrated under reduced pressure to give the title compound (S)-2-[2-(2-hydroxy-3-morpholin-4-yl-propylamino)-ethyl]-4-methyl-1H-pyrrole-3-carboxylic acid ethyl ester 1d (15.6 g, yield 96%) as a brown oil.

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 150 mL of hydrochloric acid (2N)
  5. additionwas then added to the residue
  6. addition50 mL of iced water was then added
  7. extractionextracted with ethyl acetate (200 mL ×2)
  8. washThe combined organic extracts were washed with saturated brine (100 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-4de189a2a6a646bdb6cf6813305a7a65
Source dataset
uspto-grants-2012_10
Patent number
US08299069B2

Reaction notes

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