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Chloroform → N-methoxy-N-methyl-4-nitro-2'-methoxymethoxy-6'-methoxy-biphenyl-2-carboxamide

HRID 1358113
Notes
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Reaction equation

HRID 1358113 reaction equation
C([Li])CCC.[CH3:6][O:7][C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH2:15][O:16][CH3:17])[CH:9]=1.[CH3:18][O:19][N:20]([CH3:33])[C:21](=[O:32])[C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=1Br.C(Cl)(Cl)Cl>C1COCC1.[Cl-].[Zn+2].[Cl-].[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:18][O:19][N:20]([CH3:33])[C:21]([C:22]1[C:23]([C:9]2[C:8]([O:7][CH3:6])=[CH:13][CH:12]=[CH:11][C:10]=2[O:14][CH2:15][O:16][CH3:17])=[CH:24][CH:25]=[C:26]([N+:28]([O-:30])=[O:29])[CH:27]=1)=[O:32]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 6212ChloroformHCID 5426211-Methoxy-3-(methoxymethoxy)benzeneHCID 18188772N-methoxy-N-methyl-2-bromo-5-nitrobenzamideHCID 178418339Butyllithium

Product 1

HCID 18189308N-methoxy-N-methyl-4-nitro-2'-methoxymethoxy-6'-methoxy-biphenyl-2-carboxamideYield 88%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalyst
HCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalyst
HCID 8028TetrahydrofuranSolvent2×

Procedure

Butyllithium (8.28 ml. of 2.5M in hexane, 20.69 mmole) was added to a solution of 1-methoxy-3 methoxymethoxy benzene (3.62 g., 21.55 mmole, (T. Kaufman, R. Srivastava, R. Sindelar, J. Med. Chem. 1995, 38, 1437-1445) in. THF (15 mL) at −30° C. The solution was stirred at ambient temperature for 1 hour, cooled to at 0° C. and anhydrous zinc chloride beads (3.5 g, 25.67 mmole) added. The mixture was stirred for 2 hours at 25°. Then a solution of N-methoxy-N-methyl-2-bromo-5-nitrobenzamide (5.00 g, 17.24 mmole) dissolved in THF (20 mL) was added. Bis (triphenylphosphine) palladium dichloride (600 mg.) was added and the solution was stirred at 65° C. for 15 hours. After cooling, chloroform was added and the solution stirred with aqueous KHCO3. The precipitated zinc salts were filtered, the water layer removed and the organic layer dried (Na2SO4), filtered concentrated under reduced pressure and the residuepurified on silica gel eluting with 8% ethyl acetate in CH2Cl2 to provide the titled compound (5.68 g, 88% yield).

Workup

  1. customat −30° C
  2. additionadded
  3. stirringThe mixture was stirred for 2 hours at 25°
  4. additionwas added
  5. stirringthe solution was stirred at 65° C. for 15 hours
  6. temperatureAfter cooling
  7. filtrationThe precipitated zinc salts were filtered
  8. customthe water layer removed
  9. dry with materialthe organic layer dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-648bf1047d70405d923fd46975cfcfba
Source dataset
uspto-grants-2003_07
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US06593480B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes