Hydrochloric Acid → (S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(methoxycarbonylamino)propanoate

HRID 20866Notes

Reaction equation

HRID 20866 reaction equation
[CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][C@H:14]([NH:25][C:26]([O:28][C:29](C)(C)C)=[O:27])[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O.C([O-])(O)=O.[Na+].ClC(OC)=O.Cl>C(Cl)Cl.C1COCC1.O.O.CCOC(C)=O>[CH2:1]([N:8]1[CH:12]=[C:11]([CH2:13][C@H:14]([NH:25][C:26]([O:28][CH3:29])=[O:27])[C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[N:10]=[N:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 6586Methyl chloroformateHCID 516892Sodium BicarbonateHCID 59166425(S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(tert-butoxycarbonylamino)propanoate

Product 1

HCID 71182684(S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(methoxycarbonylamino)propanoate

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 21881883Oxolane--water (1/1)SolventHCID 22728543Water ethylacetateSolvent

Procedure

A solution of (S)-benzyl 3-(1-benzyl-1H-1,2,3-triazol-4-yl)-2-(tert-butoxycarbonylamino)propanoate (0.52 g, 1.15 mmol) in CH2Cl2 was added TFA (4 mL). The mixture was allowed to stir at room temperature for 2 h. The mixture was concentrated in vacuo to give a colorless oil which solidified on standing. This material was dissolved in THF-H2O and cooled to 0° C. Solid NaHCO3 (0.25 g, 3.00 mmol) was added followed by ClCO2Me (0.25 mL, 3.25 mmol). After stirring for 1.5 h the mixture was acidified to pH ˜2 with 6N HCl and then poured into H2O-EtOAc. The layers were separated and the aq phase extracted 2× with EtOAc. The combined org layers were washed (H2O, brine), dried (Na2SO4), filtered, and concentrated in vacuo to give a colorless oil (505.8 mg, 111%, NMR suggested the presence of an unidentified impurity) which solidified while standing on the pump. The material was used as is without further purification. 1HNMR (400 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.70 (d, J=8.1 Hz, 1H), 7.27-7.32 (m, 10H), 5.54 (s, 2H), 5.10 (d, J=12.7 Hz, 1H), 5.06 (d, J=12.7 Hz, 1H), 4.32-4.37 (m, 1H), 3.49 (s, 3H), 3.09 (dd, J=5.6, 14.7 Hz, 1H), 2.98 (dd, J=9.6, 14.7 Hz, 1H). LCMS: Anal. Calcd. for C21H22N4O4: 394; found: 395 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. customto give a colorless oil which
  3. temperaturecooled to 0° C
  4. stirringAfter stirring for 1.5 h the mixture
  5. customThe layers were separated
  6. extractionthe aq phase extracted 2× with EtOAc
  7. washThe combined org layers were washed (H2O, brine)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customto give a colorless oil (505.8 mg, 111%, NMR
  12. customas is without further purification

Sources & evidence

ORD record
ord-3e31dded6ab1480893403370a070f245
Source dataset
uspto-grants-2010_06
Patent number
US07745636B2

Reaction notes

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