Cesium carbonate → [2-(4-Amino-3-nitro-phenyl)-ethyl]-carbamic acid benzyl ester

HRID 1777767

Reaction equation

HRID 1777767 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1.[CH2:12]([O:19][C:20]([NH:22][CH2:23][CH2:24][B-](F)(F)F)=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.CC(=O)OCC.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:12]([O:19][C:20](=[O:21])[NH:22][CH2:23][CH2:24][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([N+:9]([O-:11])=[O:10])[CH:3]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 701324-Bromo-2-nitroanilineHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 49761741Potassium benzyl N-[2-(trifluoroboranuidyl)ethyl]carbamate

Product 1

HCID 89726349[2-(4-Amino-3-nitro-phenyl)-ethyl]-carbamic acid benzyl esterYield 19.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 8857Ethyl AcetateSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A flask was charged with 4-bromo-2-nitroaniline (505 mg), potassium (2-(((benzyloxy)carbonyl)amino)ethyl)trifluoroborate (745 mg), Pd(OAc)2 (25.3 mg), 2-(dicyclohexylphosphino)-2′,6′-dimethoxybiphenyl (94.6 mg) and Cs2CO3 (2.2 g) in dioxane/water (20 mL/2 mL). The reaction mixture was refluxed for 92 h, cooled down, diluted with EA and washed with water and brine. The aq. layers were extracted with EA, the combined org. layers were dried (MgSO4), filtered off and evaporated to dryness. The residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 10 for 3CV, 10 to 30 over 3CV, 30 for 4CV, 30 to 50 over 3CV, 50 for 5CV) to afford 143 mg of red oil. LC-MS (B): tR=0.85 min; [M]+: 316.07.

Workup

  1. temperatureThe reaction mixture was refluxed for 92 h
  2. temperaturecooled down
  3. washwashed with water and brine
  4. extractionThe aq. layers were extracted with EA
  5. dry with materiallayers were dried (MgSO4)
  6. filtrationfiltered off
  7. customevaporated to dryness
  8. customThe residue was purified by CC (Biotage, SNAP 25 g cartridge, solvent A: Hept; solvent B: EA; gradient in % B: 10 for 3CV, 10 to 30 over 3CV, 30 for 4CV, 30 to 50 over 3CV, 50 for 5CV)

Sources & evidence

ORD record
ord-be6342ebe1c8468a9fe891ac623a9f69
Source dataset
uspto-grants-2016_02
Patent number
US09266876B2

Linked notes

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