Hydrochloric Acid → (S)-tert-Butyl 2-(((S)-1-amino-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate

HRID 1586695Notes

Reaction equation

HRID 1586695 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.CN1CCOCC1.ClC(OCC(C)C)=O.Cl.[NH2:32][C@H:33]([C:41]([NH2:43])=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>C(OCC)(=O)C.CC(N(C)C)=O>[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:32][C@H:33]([C:41]([NH2:43])=[O:42])[CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:5]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 445694Phenylalanine amide

Product 1

HCID 10861347(S)-tert-Butyl 2-(((S)-1-amino-1-oxo-3-phenylpropan-2-yl)carbamoyl)pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 31374DimethylacetamideSolvent

Conditions

Temperature
-15 °C

Procedure

To a solution of Boc-Pro-OH (4.304 g, 20 mmoles) in ethyl acetate (200 mL) at -15° C., N-methylmorpholine (2.2 mL, 20 mmoles) and isobutyl chloroformate (2.6 mL, 20 mmoles) were added. After an activation time of 10 minutes at -15° C., a solution of HCl.Phe-NH2 (4.014 g, 20 mmoles) and N-methylmorpholine (2.2 mL, 20 mmoles) in dimethylacetamide (20 mL) was added. The reaction mixture was stirred at -15° C. for 30 minutes and allowed to warm to room temperature. After stirring for 2 hours at room temperature, the reaction mixture was quenched with 10% potassium carbonate solution (30 mL). The two clear layers were transferred to a separatory funnel, and the organic layer was washed successively with 10% potassium carbonate solution (2×30 mL), saturated sodium chloride solution (1×30 mL), IN HCl (2×30 mL) and saturated sodium chloride solution (2× 30 mL). After drying over anhydrous sodium sulfate, the organic solution was filtered and concentrated on a rotary evaporator under house vacuum. The product was precipitated with hexane, filtered and dried.

Workup

  1. customAfter an activation time of 10 minutes
  2. customat -15° C.
  3. temperatureto warm to room temperature
  4. stirringAfter stirring for 2 hours at room temperature
  5. customthe reaction mixture was quenched with 10% potassium carbonate solution (30 mL)
  6. customThe two clear layers were transferred to a separatory funnel
  7. washthe organic layer was washed successively with 10% potassium carbonate solution (2×30 mL), saturated sodium chloride solution (1×30 mL), IN HCl (2×30 mL)
  8. dry with materialAfter drying over anhydrous sodium sulfate
  9. filtrationthe organic solution was filtered
  10. concentrationconcentrated on a rotary evaporator under house vacuum
  11. customThe product was precipitated with hexane
  12. filtrationfiltered
  13. customdried

Sources & evidence

ORD record
ord-62d24dc7961e4ceca2ada634e0d2e7ea
Source dataset
uspto-grants-1993_06
Patent number
US05215964

Reaction notes

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