Hydrochloric Acid → EtOCO-D,L-Phe(alphaMe)-Pro-OBzl

HRID 1648378Notes

Reaction equation

HRID 1648378 reaction equation
[CH2:1]([O:3][C:4]([NH:6][C:7]([CH3:18])([C:15]([OH:17])=O)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)=[O:5])[CH3:2].C1C=CC2N(O)N=NC=2C=1.[NH:29]1[CH2:43][CH2:42][CH2:41][C@H:30]1[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32].Cl.C(N(CC)C(C)C)(C)C.CN(C)CCCN=C=NCC.Cl>CN(C)C=O>[CH2:1]([O:3][C:4]([NH:6][C:7]([CH3:18])([C:15]([N:29]1[CH2:43][CH2:42][CH2:41][C@H:30]1[C:31]([O:33][CH2:34][C:35]1[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=1)=[O:32])=[O:17])[CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)=[O:5])[CH3:2]

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733413Proline benzyl ester hydrochlorideHCID 20192757EtOCO-D,L-Phe(alphaMe)-OH

Product 1

HCID 131719051EtOCO-D,L-Phe(alphaMe)-Pro-OBzlYield 75.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirring solution of EtOCO-D,L-Phe(αMe)-OH (10.3 g, 41 mmol), HOBT (5.5 g, 41 mmol), Pro-OBzl.HCl (9.9 g, 41 mmol) and N,N-diisopropylethylamine (15.9 g, 123 mmol) in dimethylformamide (200 mL) at 0° C., was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide.HCl (8.6 g, 45 mmol). After stirring for 16 h, the solvents were removed in vacuo and the residue was dissolved in ethyl acetate (500 mL). The organic phase was washed three times with 0.1N HCl, three times with saturated aqueous NaHCO3, and once with brine. The organic phase was then dried (Na2SO4), filtered and concentrated in vacuo. The residue was chromatographed over silica gel eluting with 1:1 ethyl acetate:hexanes and the product containing fractions (as judged by TLC) were combined and concentrated in vacuo to give 13.5 g (75% yield) of a white foam.

Workup

  1. customthe solvents were removed in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (500 mL)
  3. washThe organic phase was washed three times with 0.1N HCl, three times with saturated aqueous NaHCO3
  4. dry with materialThe organic phase was then dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed over silica gel eluting with 1:1 ethyl acetate
  8. additionhexanes and the product containing fractions (as judged by TLC)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0cf8cff6890244419df77f5bed62b811
Source dataset
uspto-grants-1995_07
Patent number
US05436229

Reaction notes

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