Dimethylformamide → 2-(2-tert-butoxycarbonylamino-ethyl)-5-formyl-4-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester

HRID 905772Notes

Reaction equation

HRID 905772 reaction equation
CN(C)[CH:3]=[O:4].P(Cl)(Cl)(Cl)=O.[CH2:11]([O:13][C:14]([C:16]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:19][NH:18][C:17]=1[CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])=[O:15])[CH3:12].[OH-].[Na+]>ClCCl.O>[CH2:11]([O:13][C:14]([C:16]1[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[C:19]([CH:3]=[O:4])[NH:18][C:17]=1[CH2:27][CH2:28][NH:29][C:30]([O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[O:31])=[O:15])[CH3:12]

Participants

7

Reactant 4

HCID 6228DimethylformamideHCID 14798Sodium HydroxideHCID 24813Phosphorus oxychlorideHCID 666087112-(2-tert-butoxycarbonylamino-ethyl)-4-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester

Product 1

HCID 866376792-(2-tert-butoxycarbonylamino-ethyl)-5-formyl-4-phenyl-1H-pyrrole-3-carboxylic acid ethyl esterYield 81.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-10 °C

Procedure

A stirred solution of dichloromethane (5.5 ml) and N,N-dimethylformamide (0.2 ml) was added dropwise slowly with phosphorus oxychloride (0.184 ml, 2 mmol) under an argon atmosphere while maintaining the temperature at −10° C.˜0° C. Upon completion of the addition, the mixture was stirred for 15 minutes at −10° C., added with the solution of 2-(2-tert-butoxycarbonylamino-ethyl)-4-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester (0.36 g, 1 mmol) in dichloromethane (2 ml) while maintaining the temperature at −10° C.˜0° C. for 1 hour. Then the mixture was stirred for another 2.5 hours at room temperature, added with cold water, adjusted to pH 11˜12 with 10% aqueous sodium hydroxide solution, extracted with ethyl acetate (50 ml×6), washed with brine, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 2-(2-tert-butoxycarbonylamino-ethyl)-5-formyl-4-phenyl-1H-pyrrole-3-carboxylic acid ethyl ester (309 mg, 81.9%) as a red oil.

Workup

  1. temperaturewhile maintaining the temperature at −10° C.˜0° C
  2. additionUpon completion of the addition
  3. temperaturewhile maintaining the temperature at −10° C.˜0° C. for 1 hour
  4. stirringThen the mixture was stirred for another 2.5 hours at room temperature
  5. extractionextracted with ethyl acetate (50 ml×6)
  6. washwashed with brine
  7. dry with materialdried with anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fbddbf8a2a3c41329b208569b8de3e78
Source dataset
uspto-grants-2011_09
Patent number
US08012966B2

Reaction notes

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