Citric Acid → 4-(4-(((2-((Tert-butoxy)carbonylamino)-1-(methoxycarbonyl)ethyl) amino)sulfonyl)-3,5-dimethylphenoxy)butanoic acid

HRID 1672094Notes

Reaction equation

HRID 1672094 reaction equation
Cl[S:2]([C:5]1[C:17]([CH3:18])=[CH:16][C:8]([O:9][CH:10]([CH2:14][CH3:15])C(O)=O)=[CH:7][C:6]=1[CH3:19])(=[O:4])=[O:3].[NH2:20][C@H:21]([C:31]([O:33][CH3:34])=[O:32])[CH2:22][NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25].Cl.[C:36]([O-])([OH:38])=[O:37].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>O1CCOCC1.O.CCOC(C)=O>[C:27]([O:26][C:24]([NH:23][CH2:22][CH:21]([NH:20][S:2]([C:5]1[C:6]([CH3:19])=[CH:7][C:8]([O:9][CH2:10][CH2:14][CH2:15][C:36]([OH:38])=[O:37])=[CH:16][C:17]=1[CH3:18])(=[O:3])=[O:4])[C:31]([O:33][CH3:34])=[O:32])=[O:25])([CH3:30])([CH3:29])[CH3:28]

Participants

8

Reactant 4

HCID 311Citric AcidHCID 516892Sodium BicarbonateHCID 18334328methyl (2S)-2-amino-3-{[(tert-butoxy)carbonyl]amino}propanoate hydrochlorideHCID 866252004-(Chlorosulfonyl)-3,5-dimethylphenoxybutanoic acid2×

Product 1

HCID 218814944-(4-(((2-((Tert-butoxy)carbonylamino)-1-(methoxycarbonyl)ethyl) amino)sulfonyl)-3,5-dimethylphenoxy)butanoic acidYield 87%

Reagents, catalysts & solvents 3

HCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of the 4-(chlorosulfonyl)-3,5-dimethylphenoxybutanoic acid, 18 (2.50 g, 8.1 mmol) in dioxane (60.0 g) was added dropwise over a period of about 45 minutes to a mixture of H-Dap(Boc)-OMe.HCl (19) (1.66 g, 6.5 mmol) (Bachem) and NaHCO3 (8.21 g, 97.7 mmol) in water (20.0 g) at rt. Two hours after completion of the addition, the reaction mixture was concentrated in vacuo then water and citric acid (12.50 g, 10.0 eq.) were added. The crude product was extracted with EtOAc and the EtOAc layer was washed once with water. Concentration of the EtOAc layer gave 2.75 g of 20 (87% yield based on 19, 69% based on 18).

Workup

  1. additionTwo hours after completion of the addition
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. extractionThe crude product was extracted with EtOAc
  4. washthe EtOAc layer was washed once with water

Sources & evidence

ORD record
ord-92bf9ef567e44a5a8925e81d2dcb8267
Source dataset
uspto-grants-2011_08
Patent number
US07998462B2

Reaction notes

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