Triethylamine → (1S,4S)-5-(4-methoxy-3-nitro-phenyl)-2-oxa-5-aza-bicyclo[2.2.1]heptane

HRID 51849Notes

Reaction equation

HRID 51849 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[C:4]([N+:10]([O-:12])=[O:11])[CH:3]=1.Cl.[C@H:14]12[CH2:20][C@H:17]([O:18][CH2:19]1)[CH2:16][NH:15]2.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].C(N(CC)CC)C>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([N:15]2[CH2:16][C@@H:17]3[CH2:20][C@H:14]2[CH2:19][O:18]3)=[CH:3][C:4]=1[N+:10]([O-:12])=[O:11]

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 10796Cesium carbonateHCID 1185334-Bromo-2-nitroanisoleHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 21303398(1S,4S)-2-oxa-5-azabicyclo(2.2.1)heptane hydrochloride

Product 1

HCID 69922496(1S,4S)-5-(4-methoxy-3-nitro-phenyl)-2-oxa-5-aza-bicyclo[2.2.1]heptaneYield 66%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a stirred solution of 7.34 g (31.0 mmol) 4-bromo-2-nitro-anisole in 125 ml dioxane were added 5.25 g (37.2 mmol) (1S,4S)-(+)-2-aza-5-oxabicyclo[2,2,1]heptane hydrochloride, 1.109 g (3.10 mmol) 2-(dicyclohexylphosphino)biphenyl, 14.2 g (43.4 mmol) cesium carbonate, 696 mg (3.10 mmol) palladium (II) acetate and 5.65 ml (40.3 mmol) triethylamine. The mixture was heated at reflux for 24 h and then poured onto water and extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and concentrated in vacuo. Flash chromatography (1/99 methanol/dichloromethane) afforded 5.10 g (66%) (1S,4S)-5-(4-methoxy-3-nitro-phenyl)-2-oxa-5-aza-bicyclo[2.2.1]heptane as an orange oil. ES-MS m/e (%): 251 (M+H+, 100).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 24 h
  3. additionpoured onto water
  4. extractionextracted three times with ethyl acetate
  5. dry with materialThe combined organic phases were dried over sodium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a49600020628495eae1133039a7c0ebf
Source dataset
uspto-grants-2004_03
Patent number
US06713499B2

Reaction notes

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