Ammonium Chloride → 2-Cyclohexyl-2-hydroxy-2-phenylacetic Acid (3R)-1-azabicyclo[2.2.2]oct-3-yl Ester

HRID 1244462Notes

Reaction equation

HRID 1244462 reaction equation
[CH:1]1([Mg]Cl)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[N:9]12[CH2:16][CH2:15][CH:12]([CH2:13][CH2:14]1)[C@@H:11]([O:17][C:18](=[O:27])[C:19](=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[CH2:10]2.[Cl-].[NH4+]>CCOCC.C1COCC1>[N:9]12[CH2:14][CH2:13][CH:12]([CH2:15][CH2:16]1)[C@@H:11]([O:17][C:18](=[O:27])[C:19]([CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1)([OH:26])[C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1)[CH2:10]2

Participants

6

Reactant 3

HCID 25517Ammonium ChlorideHCID 228507002-oxo-2-phenylacetic acid (3R)-1-azabicyclo[2.2.2]oct-3-yl esterHCID 178478990HCID 178478990, compound

Product 1

HCID 543289522-Cyclohexyl-2-hydroxy-2-phenylacetic Acid (3R)-1-azabicyclo[2.2.2]oct-3-yl Ester

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

Cyclohexylmagnesium cloride, 0.127 mol (63.6 ml of a solution 2M in ether), was added to a solution of 28.7 g (0.111 mol) of 2-oxo-2-phenylacetic acid (3R)-1-azabicyclo[2.2.2]oct-3-yl ester dissolved in 350 ml of THF, at −70° C. under a N2 atmosphere. The mixture was stirred at this temperature for 10 minutes, and then warmed to room temperature. After 1 h, the reaction mixture was treated with a saturated solution of ammonium chloride and extracted twice with ethyl acetate. The organic phases were combined, washed with water, and dried over MgSO4. After removal of the solvent, the oil obtained (27.0 g) was purified by chromatography on silica gel eluting with chloroform/methanol 10:1. The yield was 18.7 g (49.2%) of a pure product, mixture of diastereomers: I-16a and I-16b.

Workup

  1. waitAfter 1 h
  2. extractionextracted twice with ethyl acetate
  3. washwashed with water
  4. dry with materialdried over MgSO4
  5. customAfter removal of the solvent
  6. customthe oil obtained (27.0 g)
  7. customwas purified by chromatography on silica gel eluting with chloroform/methanol 10:1
  8. additionThe yield was 18.7 g (49.2%) of a pure product, mixture of diastereomers

Sources & evidence

ORD record
ord-4cc93856a11b41388cb102f368686470
Source dataset
uspto-grants-2006_10
Patent number
US07122558B2

Reaction notes

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