Sodium Iodide → (3S)-1-[N-[3-[[(t-Butyloxy)carbonyl]amino]-2-oxo-4-phenylbutyl]-N-[(phenylmethoxy)carbonyl]-L-alanyl]-L-proline, t-butyl ester

HRID 652346

Reaction equation

HRID 652346 reaction equation
[C:1]([O:5][C:6](=[O:17])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:16])[C@H:13]([CH3:15])[NH2:14])([CH3:4])([CH3:3])[CH3:2].Cl[CH2:19]C(CCl)=O.[C:24]([O:28][C:29]([NH:31][C@H:32]([C:40]([OH:42])=O)[CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)=[O:30])([CH3:27])([CH3:26])[CH3:25].C(=O)(O)[O-].[Na+].[I-].[Na+].[CH2:50]([O:57][C:58](Cl)=[O:59])[C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1>CN(C)C=O>[C:24]([O:28][C:29]([NH:31][C@@H:32]([CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)[C:40](=[O:42])[CH2:19][N:14]([C:58]([O:57][CH2:50][C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)=[O:59])[C@H:13]([C:12]([N:8]1[CH2:9][CH2:10][CH2:11][C@H:7]1[C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:17])=[O:16])[CH3:15])=[O:30])([CH3:25])([CH3:26])[CH3:27]

Participants

7

Reactant 5

HCID 5238Sodium IodideHCID 10387Benzyl chloroformateHCID 516892Sodium Bicarbonate2×HCID 12939800tert-Butyl L-alanyl-L-prolinateHCID 88667995N-[(t-Butyloxy)carbonyl]-L-phenylalanine chloromethyl ketone

Product 1

HCID 131714417(3S)-1-[N-[3-[[(t-Butyloxy)carbonyl]amino]-2-oxo-4-phenylbutyl]-N-[(phenylmethoxy)carbonyl]-L-alanyl]-L-proline, t-butyl esterYield 51.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of L-alanyl-L-proline t-butyl ester (1.0 g, 4.13 mmol), N-[(t-butyloxy)carbonyl]-L-phenylalanine chloromethyl ketone (1.2 g, 4.03 mmol), sodium bicarbonate (370 mg, 4.4 mmol) and sodium iodide (300 mg, 2 mmol) in dimethylformamide (7 ml) was stirred overnight at room temperature. The reaction mixture was evaporated. Dioxane (6 ml) was added to the residue followed by benzyloxycarbonyl chloride (0.75 ml, 5.24 mmol) and sodium bicarbonate (500 mg, 5.95 mmol). After stirring overnight, the reaction mixture was evaporated, the residue taken up in ethyl acetate and washed neutral (water, saturated sodium bicarbonate solution, water, 10% potassium bisulfate solution and water). The crude material (2.6 g) was chromatographed over silica gel (200 g) using the solvent system ethyl acetate:benzene-1:3 to obtain 1.32 g of the title compound.

Workup

  1. customThe reaction mixture was evaporated
  2. additionDioxane (6 ml) was added to the residue
  3. customthe reaction mixture was evaporated
  4. washwashed neutral (water, saturated sodium bicarbonate solution, water, 10% potassium bisulfate solution and water)
  5. customThe crude material (2.6 g) was chromatographed over silica gel (200 g)

Sources & evidence

ORD record
ord-d770e609b9924213b201fbf0c6f09e4d
Source dataset
uspto-grants-1987_06
Patent number
US04670541

Linked notes

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