Methyl Isocyanate → HCID 22050943, compound

HRID 1866955Notes

Reaction equation

HRID 1866955 reaction equation
N=C=N.[CH3:4][O:5][CH2:6][C:7]([OH:9])=O.ON1C2C=CC=CC=2N=N1.[NH2:20][CH2:21][C:22]1[CH:23]=[C:24]([N:28]2[C:33]([CH3:34])=[CH:32][C:31]([O:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=3[F:44])=[C:30]([Br:45])[C:29]2=[O:46])[CH:25]=[CH:26][CH:27]=1.CN=C=O>CN(C)C(=O)C.CN1CCOCC1.ClCCCl>[Br:45][C:30]1[C:29](=[O:46])[N:28]([C:24]2[CH:23]=[C:22]([CH:27]=[CH:26][CH:25]=2)[CH2:21][NH:20][C:7](=[O:9])[CH2:6][O:5][CH3:4])[C:33]([CH3:34])=[CH:32][C:31]=1[O:35][CH2:36][C:37]1[CH:42]=[CH:41][C:40]([F:43])=[CH:39][C:38]=1[F:44]

Participants

9

Reactant 5

HCID 12228Methyl IsocyanateHCID 12251Methoxyacetic AcidHCID 757711-HydroxybenzotriazoleHCID 160435CarbodiimideHCID 22051179HCID 22051179, compound

Product 1

HCID 22050943HCID 22050943, compoundYield 28%

Reagents, catalysts & solvents 3

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

Procedure

To a reaction vessel (borosilicate culture tube) was added approximately 2.87 g of polymer bound carbodiimide resin (0.96 mmol/g) followed by a stock solution of methoxyacetic acid (8.0 mL, 0.10 M) in N,N-dimethylacetamide. A stock solution of 1-hydroxybenzotriazole in N,N-dimethylacetamide (3.0 mL, 0.10 M) and N-methylmorpholine (6.0 mL, 0.10 M) in 1,2-dichloroethane 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 4 hours. A stock solution of EXAMPLE 293 in N,N-dimethylacetamide (5.0 mL, 0.10 M) 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 (10 mL) and treated with approximately 1.70 g of polyamine resin (2.63 mmol/g) and approximately 0.84 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). The filtrate was evaporated 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) afforded an off white solid (0.081 g, 28%). 1H NMR (400 MHz, DMF-d6) δ 7.59 (q, J=7.65 Hz, 1H), 7.46 (app t, J=7.55 Hz, 1H), 7.40-7.37 (m, 1H), 7.11-7.07 (m, 2H), 7.00 (t, J=8.56 Hz, 2H), 6.54 (s, 1H), 5.30 (s, 2H), 4.43 (s, 2H), 3.88 (s, 2H), 3.35 (app d, J=0.80 Hz, 2H), 1.97 (s, 3H). ES-HRMS m/z 507.0699 (M+H C23H21BrF2N2O4 requires 507.0726).

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. customThe filtrate was evaporated
  8. temperatureheating (60° C.) in a reaction block (KEM-Lab Parallel Reactor)

Sources & evidence

ORD record
ord-f1715b834a8c403ab8f6b49ce87c7344
Source dataset
uspto-grants-2009_12
Patent number
US07629363B2

Reaction notes

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