Benzyl Alcohol → 1-Tert-butyloxycarbonyl-trans-3-benzyloxycarbonylamino-4-(2-pyridyl)pyrrolidine

HRID 398399Notes

Reaction equation

HRID 398399 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10](C(O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC[N:24]([CH:28](C)C)C(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:38])C=CC=CC=1.[CH2:48]([OH:55])[C:49]1[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=1>C1(C)C=CC=CC=1.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=2)[C@H:10]([NH:24][C:28]([O:55][CH2:48][C:49]2[CH:54]=[CH:53][CH:52]=[CH:51][CH:50]=2)=[O:38])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 244Benzyl AlcoholHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 2762196Boc-trans-4-(2-pyridinyl)-pyrrolidine-3-carboxylic acid

Product 1

HCID 700235531-Tert-butyloxycarbonyl-trans-3-benzyloxycarbonylamino-4-(2-pyridyl)pyrrolidine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 1-tert-butyloxycarbonyl-trans-4-(2-pyridyl)pyrrolidine-3-carboxylic acid from step 5 above (13 mmol) in toluene (50 mL) was added DIEA (3.0 mL, 17 mmol). The solution was cooled to 0° C. and diphenylphosphoryl azide (4.1 g, 15 mmol) was added. The resulting solution was stirred at 0° C. for 1 h and at ambient temperature for 4 h. Benzyl alcohol (2.8 g, 26 mmol) was added and the solution was refluxed for 3 h. The solution was cooled to ambient temperature, diluted with EtOAc, and washed with aqueous NaHCO3. The organic phase was separated, dried over MgSO4, filtered, and the solvents were removed in vacuo. The residue was purified by flash column chromatography using a gradient elution of 10-25% EtOAc:hexanes to give the title compound as an oil (3.9 g, TLC Rf=0.4, 1:3 EtOAc-hexanes; HPLC RT=6.67 min, method A).

Workup

  1. temperaturethe solution was refluxed for 3 h
  2. temperatureThe solution was cooled to ambient temperature
  3. washwashed with aqueous NaHCO3
  4. customThe organic phase was separated
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvents were removed in vacuo
  8. customThe residue was purified by flash column chromatography
  9. washa gradient elution of 10-25% EtOAc

Sources & evidence

ORD record
ord-e8b46c32a3784204809afd97ef45b796
Source dataset
uspto-grants-2003_08
Patent number
US06610692B1

Reaction notes

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