Hydrochloric Acid → HCID 14308498, compound

HRID 1481658Notes

Reaction equation

HRID 1481658 reaction equation
[N:1]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([OH:5])=O.ClC(OCC(C)C)=O.Cl.[NH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28]>C(Cl)Cl.C(Cl)(Cl)Cl.CCOCC>[N:1]1([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH2:8][CH2:7][CH2:6][C@H:2]1[C:3]([NH:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:5]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 12176Glycine ethyl esterHCID 62365Isobutyl chloroformateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-

Product 1

HCID 14308498HCID 14308498, compound

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
5 °C

Procedure

8.3 g (3.45 mmol) of Boc-Pro-OH were dissolved in 50 ml of CH2Cl2, cooled down to 5° C.; then, 38.45 mmol (5.38 ml) of TEA were added. The reaction mixture was cooled down to −25÷−30° C. At this temperature, 38.45 mmol (4.84 ml) of isobutyl chloroformate were added using a pipette. The reaction mixture temperature was kept in the range of −18÷−20° C. for 20 minutes. Simultaneously, a solution of 5.9 g (42.3 mmol) of 1.1-fold excess of HCl.H-Gly-OEt in 75 ml of chloroform, containing 5.92 ml of TEA. The solution was cooled down to −25° C. and, after formation of mixed anhydride in the first flask, its contents were poured to the ether solution right away. The reaction mixture was incubated for 1 hour at −10° C. and then stirred for 12 hours at 4° C. on a magnetic stirrer. The reaction mixture was evaporated, then 250 ml of ethyl acetate were added; then, ethyl acetate solution was washed 3 times with 25 ml of 0.1N HCl, 3 times with 25 ml H2O, and once with saturated solution of NaCl. The organic layer was dried over MgSO4, filtered and evaporated. The residue was dried under vacuum over P2O5/KOH and paraffin.

Workup

  1. temperatureThe reaction mixture was cooled down to −25÷−30° C
  2. temperatureThe solution was cooled down to −25° C.
  3. waitThe reaction mixture was incubated for 1 hour at −10° C.
  4. customThe reaction mixture was evaporated
  5. addition250 ml of ethyl acetate were added
  6. washthen, ethyl acetate solution was washed 3 times with 25 ml of 0.1N HCl, 3 times with 25 ml H2O
  7. dry with materialThe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. dry with materialThe residue was dried under vacuum over P2O5/KOH and paraffin

Sources & evidence

ORD record
ord-281c3017495b4701812a6f978a4a3244
Source dataset
uspto-grants-2016_08
Patent number
US09409947B2

Reaction notes

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