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

HRID 1672095Notes

Reaction equation

HRID 1672095 reaction equation
[NH2:1][C@H:2]([C:12]([O:14][CH3:15])=[O:13])[CH2:3][NH:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].Cl.[C:17]([O-:20])(O)=[O:18].[Na+].Cl[S:23]([C:26]1[C:38]([CH3:39])=[CH:37][C:29]([O:30][CH:31]([CH2:35][CH3:36])C(O)=O)=[CH:28][C:27]=1[CH3:40])(=[O:25])=[O:24]>O1CCOCC1>[C:8]([O:7][C:5]([NH:4][CH2:3][CH:2]([NH:1][S:23]([C:26]1[C:27]([CH3:40])=[CH:28][C:29]([O:30][CH2:31][CH2:35][CH2:36][C:17]([OH:20])=[O:18])=[CH:37][C:38]=1[CH3:39])(=[O:25])=[O:24])[C:12]([O:14][CH3:15])=[O:13])=[O:6])([CH3:11])([CH3:10])[CH3:9]

Participants

5

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

A slurry of H-Dap(Boc)-OMe.HCl (19) (8.0 g, 31.4 mmol) and NaHCO3 (38.6 g, 460 mmol) in 140 mL dioxane/28 mL H2O was cooled to 5° C. with an ice bath. To this slurry was added a solution of the 4-(chlorosulfonyl)-3,5-dimethylphenoxybutanoic acid, 18 (14.0 g 46 mmol) in dioxane (140 mL) dropwise over a period of 75 minutes. After an additional 2 hr the reaction mixture was filtered and the filtrate concentrated in vacuo. To the residue was added water (total volume of 420 mL) and then this was extracted with 75 mL MTBE. The aqueous phase was made acidic (pH=4) using 3 N HCl (aq.) then extracted with EtOAc (300 mL). The EtOAc extract was dried over Na2SO4, filtered and concentrated in vacuo leaving 10.2 g of desired product, 20 (20.9 mmol, 66.5% based on 19, 45% based on 18).

Workup

  1. filtrationAfter an additional 2 hr the reaction mixture was filtered
  2. concentrationthe filtrate concentrated in vacuo
  3. additionTo the residue was added water (total volume of 420 mL)
  4. extractionthis was extracted with 75 mL MTBE
  5. extractionthen extracted with EtOAc (300 mL)
  6. extractionThe EtOAc extract
  7. dry with materialwas dried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e2111e23e6c54793afe25daeb9efb300
Source dataset
uspto-grants-2011_08
Patent number
US07998462B2

Reaction notes

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