Triethylamine → alpha-Azavalinyl-(L)-proline t-butyl ester

HRID 979956Notes

Reaction equation

HRID 979956 reaction equation
[C:1]([O:5][C:6](=[O:15])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](Cl)=[O:13])([CH3:4])([CH3:3])[CH3:2].C([NH:26][NH:27][CH:28]([CH3:30])[CH3:29])(OCC1C=CC=CC=1)=O.C(N(CC)CC)C>C1COCC1>[C:1]([O:5][C:6](=[O:15])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:13])[N:27]([CH:28]([CH3:30])[CH3:29])[NH2:26])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 14552297Tert-butyl (2S)-1-(carbonochloridoyl)pyrrolidine-2-carboxylateHCID 15732457N-Carbobenzyloxy-N'-isopropylhydrazine

Product 1

HCID 70474195alpha-Azavalinyl-(L)-proline t-butyl esterYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Carbamoyl chloride 1 (4 mmol, crude), prepared as described above, was combined with carbazide 4 (3.50 mmol; 0.728 g) and triethylamine (0.557 ml; 4.00 mmol) in dry THF (2 ml). The mixture was heated at reflux for 7 hours, then filtered and evaporated to a thick oil. This was dissolved in benzene (10 ml) and hydrogenated with 10% Pd(C) (0.35 g) at 1 atm. for 6 hours. Filtration of the catalyst and evaporation gave a light yellow oil which was purified by flash chromatography on silica gel (CH2Cl2 --CH3OH, 50:1). There was obtained pure carbazide 5 (0.622 g; 2.30 mmol; 66%) as a light yellow solid. Recrystallization from hexanes gave a sample, mp 87°-91° C. TLC (silica gel; CH2Cl2 --CH3OH; 20:1) Rf=0.4. MS m/e 271 (M+). Analysis: Calculated for C13H25N 3 O3 : C, 57.54; H, 9.29; N, 15.48. Found: C, 57.67; H, 9.46; N, 15.44. NMR (CDCl3): δ1.08 (3H,d, J=6); 1.13 (3H, d, J=6); 1.43 (9H,s); 1.7-2.2 (4H,m); 2.4-2.7 (2H,m); 3.3 (2H,bs); 4.07 (1H, septet, J=6); 4.3-4.5 (1H,m). lR(CHCl3): 3600-3300, 1730, 1630 cm-1. [α]D =15.9°±b 0.5°. [α]d =15.9°±0.5°.

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 7 hours
  3. filtrationfiltered
  4. customevaporated to a thick oil
  5. dissolutionThis was dissolved in benzene (10 ml) and hydrogenated with 10% Pd(C) (0.35 g) at 1 atm. for 6 hours
  6. filtrationFiltration of the catalyst and evaporation
  7. customgave a light yellow oil which
  8. customwas purified by flash chromatography on silica gel (CH2Cl2 --CH3OH, 50:1)

Sources & evidence

ORD record
ord-95eae1cf779445198c23bc9357d2f5ca
Source dataset
uspto-grants-1987_01
Patent number
US04634715

Reaction notes

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