Sodium Iodide → N-[N-[N-[(3S)-3-[[(t-Butyloxy)carbonyl]amino]-2-oxo-5-methylhexyl]-L-leucyl]-L-valyl]-L-phenyl-alanine, methyl ester

HRID 652350Notes

Reaction equation

HRID 652350 reaction equation
Cl.[NH2:2][C@H:3]([C:8]([NH:10][C@H:11]([C:15]([NH:17][C@H:18]([C:26]([O:28][CH3:29])=[O:27])[CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:16])[CH:12]([CH3:14])[CH3:13])=[O:9])[CH2:4][CH:5]([CH3:7])[CH3:6].[I-].[Na+].[C:32](=O)(O)[O-].[Na+].ClCC(CCl)=O.[C:43]([O:47][C:48]([NH:50][C@H:51]([C:56]([OH:58])=O)[CH2:52][CH:53]([CH3:55])[CH3:54])=[O:49])([CH3:46])([CH3:45])[CH3:44]>CN(C)C=O.C(OCC)(=O)C.CCOCC.CC(C)=O>[C:43]([O:47][C:48]([NH:50][C@@H:51]([CH2:52][CH:53]([CH3:54])[CH3:55])[C:56](=[O:58])[CH2:32][NH:2][C@H:3]([C:8]([NH:10][C@H:11]([C:15]([NH:17][C@H:18]([C:26]([O:28][CH3:29])=[O:27])[CH2:19][C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1)=[O:16])[CH:12]([CH3:14])[CH3:13])=[O:9])[CH2:4][CH:5]([CH3:7])[CH3:6])=[O:49])([CH3:44])([CH3:45])[CH3:46]

Participants

9

Reactant 4

HCID 5238Sodium IodideHCID 516892Sodium BicarbonateHCID 88640365HCID 88640365, compoundHCID 131714421HCID 131714421, compound

Product 1

HCID 13933355N-[N-[N-[(3S)-3-[[(t-Butyloxy)carbonyl]amino]-2-oxo-5-methylhexyl]-L-leucyl]-L-valyl]-L-phenyl-alanine, methyl esterYield 39.6%

Reagents, catalysts & solvents 4

HCID 180AcetoneSolventHCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 856 mg (2 mmol) of L-leucyl-L-valyl-L-phenylalanine, methyl ester, hydrochloride, 100 mg (0.668 mmol) of sodium iodide, and 352 mg (4.2 mmol) of sodium bicarbonate in 3 ml of dimethylformamide was treated with 580 mg (2.2 mmol) of [(t-butyloxy)carbonyl]-L-leucine chloromethyl ketone dissolved in 2 ml of dimethylformamide, and the reaction was stirred at room temperature under a flow of nitrogen overnight. The reaction was then diluted with a mixture of 80 ml of ethyl acetate and 20 ml of ether, then washed with 20 ml portions of water (2×), 5% aqueous sodium bisulfite, water (2×), brine, dried (magnesium sulfate), and concentrated in vacuo to afford 1.1 g of crude product. Flash chromatography on 30 g of LPS-1 silica gel eluting with a 5:1 mixture of petroleum ether:acetone afforded 680 mg of partially purified product. Recrystallization from acetone:petroleum ether afforded 490 mg of the title compound, melting point 127°-129° C.

Workup

  1. washwashed with 20 ml portions of water (2×), 5% aqueous sodium bisulfite, water (2×), brine
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated in vacuo
  4. customto afford 1.1 g of crude product
  5. customRecrystallization from acetone

Sources & evidence

ORD record
ord-ea956cb8eb56451aac18277b02877c80
Source dataset
uspto-grants-1987_06
Patent number
US04670541

Reaction notes

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