Sodium hydride → 210692-57-2

HRID 2075809Notes

Reaction equation

HRID 2075809 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][C:8]([Cl:13])=[CH:9][C:10]=2[Cl:12])[N:5]=[C:4]([C:14]([O:16][CH2:17][CH3:18])=[O:15])[CH:3]=1.[C:19]1([N:25]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[C:26](Cl)=[O:27])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1.[H-].[Na+]>CN(C)C=O>[Cl:12][C:10]1[CH:9]=[C:8]([Cl:13])[CH:7]=[C:6]2[C:11]=1[C:2]([NH:1][C:26]([N:25]([C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:27])=[CH:3][C:4]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[N:5]2

Participants

5

Reactant 3

HCID 24758Sodium hydride2×HCID 65741N,N-Diphenylcarbamic chlorideHCID 57709574HCID 57709574, compound2×

Product 1

HCID 15872008210692-57-2Yield 80.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-L three-neck flask was charged with a cold (<10° C.) solution of Compound 5 (about 0.59 mole, 168.95 g) in N,N-dimethylformamide (DMF) (about 2 L). Diphenylcarbamoyl chloride (0.73 mole, 168.92 g) then was added to the solution. The resulting mixture was maintained below 10° C., sodium hydride (NaH; 1.19 mole, 28.45 g) was added, in portions, over about 1.3 hours, and the reaction mixture was allowed to warm to ambient temperature overnight. Thin layer chromatography (TLC) indicated that some unreacted Compound 5 remained. The reaction mixture was recooled to about 10° C., and additional NaH (about 0.3 mole, 7.11 g) was added. The subsequent reaction was quenched with saturated aqueous ammonium chloride (NH4Cl; about 1.3 L) followed by the addition of 10% aqueous acetic acid (AcOH; 1 L), 20% AcOH (0.5 L), and EtOAc (4 L) to obtain a mixture having a pH of about 4 to 5. The solids present in the flask then were filtered, rinsed with EtOAc (500 mL) and DI water (500 mL), and dried by lyophilization to afford about 229 g of crude Compound 6 and a crude filtrate containing additional Compound 6. The crude Compound 6 was dissolved in dichloromethane (CH2Cl2; 3 L), back extracted with deionized (DI) water (500 mL) and brine (500 mL). The organic phase was dried over Na2SO4 (323.30 g) and filtered to afford a solution containing the bulk of the crude Compound 6.

Workup

  1. temperatureThe resulting mixture was maintained below 10° C.
  2. customwas recooled to about 10° C.
  3. customThe subsequent reaction
  4. customwas quenched with saturated aqueous ammonium chloride (NH4Cl; about 1.3 L)
  5. additionfollowed by the addition of 10% aqueous acetic acid (AcOH; 1 L), 20% AcOH (0.5 L), and EtOAc (4 L)
  6. customto obtain a mixture
  7. filtrationThe solids present in the flask then were filtered
  8. washrinsed with EtOAc (500 mL) and DI water (500 mL)
  9. customdried by lyophilization

Sources & evidence

ORD record
ord-4196a9bcc6354b9e955f035a14c808f8
Source dataset
uspto-grants-2011_04
Patent number
US07923458B2

Reaction notes

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