Sodium Hydroxide → methyl (R)-2-(3-1H-imidazol-4-ylpropionylamino)-3-(4-methoxyphenyl)propanoate

HRID 540379Notes

Reaction equation

HRID 540379 reaction equation
CCN(C(C)C)C(C)C.Cl.[CH2:11]([C:18]([OH:20])=O)[CH2:12][C:13]1[N:17]=[CH:16][NH:15][CH:14]=1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[NH2:43][C@H:44]([CH2:49][C:50]1[CH:55]=[CH:54][C:53]([O:56][CH3:57])=[CH:52][CH:51]=1)[C:45]([O:47][CH3:48])=[O:46].[OH-].[Na+]>CN(C=O)C>[NH:15]1[CH:14]=[C:13]([CH2:12][CH2:11][C:18]([NH:43][C@H:44]([CH2:49][C:50]2[CH:51]=[CH:52][C:53]([O:56][CH3:57])=[CH:54][CH:55]=2)[C:45]([O:47][CH3:48])=[O:46])=[O:20])[N:17]=[CH:16]1

Participants

7

Reactant 5

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 11241250(R)-Methyl 2-amino-3-(4-methoxyphenyl)propanoateHCID 178479756HCID 178479756, compound

Product 1

HCID 178501382methyl (R)-2-(3-1H-imidazol-4-ylpropionylamino)-3-(4-methoxyphenyl)propanoateYield 49%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

35.5 ml of DIEA are added to a solution containing 13.2 g (74.7 mmol) of desamino-histidine hydrochloride and 24 g (74.7 mmol) of TBTU in 100 ml of DMF. After stirring for 15 minutes at ambient temperature, 14.2 g (67.9 mmol) of methyl (R)-2-amino-3-(4-methoxyphenyl)-propanoate in 150 ml of DMF are added. The reaction medium is left to stir for 16 hours and then basified to pH=8-9 by introducing 1N sodium hydroxide and a saturated solution of sodium hydrogen carbonate, followed by extraction with dichloromethane. The organic phase is dried over sodium sulphate, filtered and evaporated. The crude product obtained is purified by silica gel chromatography (eluent 85/15 dichloromethane/methanol). 11.0 g in the form of an orange oil are obtained with a yield of 49%.

Workup

  1. waitThe reaction medium is left
  2. stirringto stir for 16 hours
  3. extractiona saturated solution of sodium hydrogen carbonate, followed by extraction with dichloromethane
  4. dry with materialThe organic phase is dried over sodium sulphate
  5. filtrationfiltered
  6. customevaporated

Sources & evidence

ORD record
ord-cad5a82c6e154366b59be598db2208ee
Source dataset
uspto-grants-2014_10
Patent number
US08871187B2

Reaction notes

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