Diethyl Ether → (Furan-2-yl)hydroxyphenylacetic Acid 1-azabicyclo[2.2.2]oct-3(R)-yl Ester

HRID 353068Notes

Reaction equation

HRID 353068 reaction equation
[C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:9]12[CH2:16][CH2:15][CH:12]([CH2:13][CH2:14]1)[C@@H:11]([O:17][C:18](=[O:26])[C:19](=[O:25])[C:20]1[O:21][CH:22]=[CH:23][CH:24]=1)[CH2:10]2.[Cl-].[NH4+].CCOCC>C1COCC1.N#N>[N:9]12[CH2:16][CH2:15][CH:12]([CH2:13][CH2:14]1)[C@@H:11]([O:17][C:18](=[O:26])[C:19]([C:20]1[O:21][CH:22]=[CH:23][CH:24]=1)([OH:25])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:10]2

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 665920532-fur-2-yl-2-oxoacetic acid (3R)-1-azabicyclo[2.2.2]oct-3-yl esterHCID 178418255HCID 178418255, compound

Product 1

HCID 66592103(Furan-2-yl)hydroxyphenylacetic Acid 1-azabicyclo[2.2.2]oct-3(R)-yl EsterYield 40%

Reagents, catalysts & solvents 2

HCID 947NitrogenSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

Phenylmagnesium bromide, 0.0057 mol (5.7 ml of a solution 1M in THF), was added to a solution of 1.3 g (0.0052 mol) of oxofuran-2-ylacetic acid 1-azabicyclo[2.2.2]oct-3(R)-yl ester (intermediate I-4e-) dissolved in 15 ml of THF, at −701C in N2 atmosphere. The mixture was stirred at this temperature for 10 minuts, and then warmed to room temperature. After 1 hour, the reaction mixture was treated with a saturated solution of ammonium chloride and extracted three times with ethyl acetate The organic phases were combined, washed with water and dried over Na2SO4. After removal of the solvent, the solid obtained was treated with ether and filtered to yield 0.67 g (40%) of a product whose structure was confirmed by 1H-NMR. This compound was also prepared as is described in Example I-la (Method c). The diastereomers were separated by crystallization from acetonitrile and distinguished by 1H-NMR.

Workup

  1. extractionextracted three times with ethyl acetate The organic phases
  2. washwashed with water
  3. dry with materialdried over Na2SO4
  4. customAfter removal of the solvent
  5. customthe solid obtained
  6. filtrationfiltered

Sources & evidence

ORD record
ord-3fcf776aad9f49159baebabb473ec24b
Source dataset
uspto-grants-2004_06
Patent number
US06750226B2

Reaction notes

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