Triethylamine → (S)-N-(4-amino-3-nitrophenyl)-N-ethyl-1-methyl-pyrrolidine-2-carboxamide

HRID 1091660Notes

Reaction equation

HRID 1091660 reaction equation
C(N(CC)CC)C.[CH2:8]([NH:10][C:11]1[CH:16]=[CH:15][C:14]([NH2:17])=[C:13]([N+:18]([O-:20])=[O:19])[CH:12]=1)[CH3:9].[CH3:21][N:22]1[CH2:29][CH2:28][CH2:27][C@H:23]1[C:24]([OH:26])=O.CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O>C(#N)C>[NH2:17][C:14]1[CH:15]=[CH:16][C:11]([N:10]([CH2:8][CH3:9])[C:24]([C@@H:23]2[CH2:27][CH2:28][CH2:29][N:22]2[CH3:21])=[O:26])=[CH:12][C:13]=1[N+:18]([O-:20])=[O:19]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 643474N-Methyl-L-proline2×HCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one2×HCID 19854182N1-ethyl-3-nitrobenzene-1,4-diamine

Product 1

HCID 66593822(S)-N-(4-amino-3-nitrophenyl)-N-ethyl-1-methyl-pyrrolidine-2-carboxamideYield 54.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Triethylamine (1.0 mL, 7.33 mmol) was added to a stirred solution of N1-ethyl-3-nitrobenzene-1,4-diamine (440 mg, 2.43 mmol), N-methyl-L-proline (314 mg, 2.43 mmol) and DEPBT (727 mg, 2.43 mmol) in acetonitrile (15 mL). The mixture was stirred at room temperature and further aliquots of N-methyl-L-proline (314 mg, 2.43 mmol), DEPBT (727 mg, 2.43 mmol), and triethylamine (1.0 mL, 7.33 mmol) were added after 1, 2, and 3 days. After stirring for a further 1 day, the mixture was concentrated and the residue taken up in EA (75 mL). The EA solution was extracted with water, and with 1M sodium carbonate solution (2×). The combined water and 1M sodium carbonate solution extracts were back-extracted with EA (4×) and the combined EA extracts washed with brine, dried over magnesium sulfate, and concentrated to give (S)—N-(4-amino-3-nitrophenyl)-N-ethyl-1-methyl-pyrrolidine-2-carboxamide (388 mg) as an orange/brown oil. This was hydrogenated in ethanol, using 10% palladium on carbon (153 mg) as the catalyst. After stirring overnight under a hydrogen atmosphere (balloon), the mixture was filtered through a pad of diatomaceous earth and the filtrate concentrated to give (S)—N-(3,4-diaminophenyl)-N-ethyl-1-methylpyrrolidine-2-carboxamide (335 mg).

Workup

  1. stirringAfter stirring for a further 1 day
  2. concentrationthe mixture was concentrated
  3. extractionThe EA solution was extracted with water
  4. extractionThe combined water and 1M sodium carbonate solution extracts were back-extracted with EA (4×)
  5. washthe combined EA extracts washed with brine
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-dbd4541b6dd1440591814422f36bd397
Source dataset
uspto-grants-2012_03
Patent number
US08129396B2

Reaction notes

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