Glycolic Acid → HCID 22051028, compound

HRID 1831967Notes

Reaction equation

HRID 1831967 reaction equation
N=C=N.[C:4]([OH:8])(=O)[CH2:5][OH:6].ON1C2C=CC=CC=2N=N1.Cl.[NH2:20][CH2:21][C:22]1[CH:27]=[CH:26][C:25]([N:28]2[CH:33]=[CH:32][C:31]([O:34][CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)=[C:30]([Br:42])[C:29]2=[O:43])=[CH:24][CH:23]=1.CN=C=O>CN(C)C(=O)C.CN1CCOCC1.ClCCCl>[CH2:35]([O:34][C:31]1[CH:32]=[CH:33][N:28]([C:25]2[CH:24]=[CH:23][C:22]([CH2:21][NH:20][C:4](=[O:8])[CH2:5][OH:6])=[CH:27][CH:26]=2)[C:29](=[O:43])[C:30]=1[Br:42])[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

9

Reactant 5

HCID 757Glycolic AcidHCID 12228Methyl IsocyanateHCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 22050088HCID 22050088, compound

Product 1

HCID 22051028HCID 22051028, compoundYield 21%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolvent2×HCID 79724-MethylmorpholineSolventHCID 31374DimethylacetamideSolvent3×

Procedure

To a reaction vessel (borosilicate culture tube) was added approximately 1.95 g of polymer bound carbodiimide resin (0.96 mmol/g) followed by a stock solution of glycolic acid (5.8 mL, 0.10 M) in N,N-dimethylacetamide. A stock solution of 1-hydroxybenzotriazole in N,N-dimethylacetamide (0.4 mL, 0.10 M) and N-methylmorpholine in 1,2-dichloroethane (3.9 mL, 0.10 M) were added to the reaction vessel. The parallel reaction apparatus was then orbitally shaken (Labline Benchtop Orbital Shaker) at approximately 200 RPM at room temperature for 2 hours. A stock solution of 1-[4-(aminomethyl)phenyl]-4-(benzyloxy)-3-bromopyridin-2(1H)-one hydrochloride in N,N-dimethylacetamide (0.05 M, 7.8 mL) was then added to the reaction vessel and the reaction apparatus was orbitally shaken at room temperature overnight. At this time the reaction was diluted with 1,2-dichloroethane (8 mL) and treated with approximately 1.17 g of polyamine resin (2.63 mmol/g) and approximately 0.58 g of methylisocyanate functionalized polystyrene (1.50 mmol/g) and the orbital shaking was continued at 200 RPM at room temperature for 4 hours. The reaction vessel was then opened and the solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial. After partial evaporation the insoluble byproducts were rinsed with N,N-dimethylacetamide (2×5 mL) and combined with the partially concentrated filtrate. The filtrate was concentrated by blowing N2 over the vial while heating (60° C.) in a reaction block (KEM-Lab Parallel Reactor) and subjected to chromatography (silica gel, ethyl acetate with 10% methanol/hexanes) which afforded an off white solid (0.081 g, 21%). 1H NMR (400 MHz, CD3OD) δ 7.55-7.30 (m, 10H), 6.51 (d, J=7.85 Hz, 1H), 5.37 (s, 2H), 4.52 (s, 2H), 4.08 (s, 2H). ES-HRMS m/z 443.0605 (M+H C21H19BrN2O4 requires 443.0601).

Workup

  1. stirringthe reaction apparatus was orbitally shaken at room temperature overnight
  2. stirringthe orbital shaking
  3. waitwas continued at 200 RPM at room temperature for 4 hours
  4. customthe solution phase products were separated from the insoluble quenched byproducts by filtration and collection into a vial
  5. customAfter partial evaporation the insoluble byproducts
  6. washwere rinsed with N,N-dimethylacetamide (2×5 mL)
  7. concentrationThe filtrate was concentrated
  8. temperatureheating (60° C.) in a reaction block (KEM-Lab Parallel Reactor)

Sources & evidence

ORD record
ord-073d7f7e934d4bf09cef6ba1515257b9
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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