Triphenylphosphine → 2-[(3S)-1-azabicyclo[2.2.2]octan-3-yloxy]-fluoren-9-one

HRID 902960Notes

Reaction equation

HRID 902960 reaction equation
[OH:1][C:2]1[CH:14]=[CH:13][C:12]2[C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[C:5](=[O:15])[C:4]=2[CH:3]=1.[N:16]12[CH2:23][CH2:22][CH:19]([CH2:20][CH2:21]1)[C@@H:18](O)[CH2:17]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[N:16]12[CH2:23][CH2:22][CH:19]([CH2:20][CH2:21]1)[C@H:18]([O:1][C:2]1[CH:14]=[CH:13][C:12]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:5](=[O:15])[C:4]=3[CH:3]=1)[CH2:17]2

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 813862-Hydroxyfluoren-9-oneHCID 914043-Quinuclidinol, (-)-HCID 5462977Diethyl azodicarboxylate

Product 1

HCID 112204662-[(3S)-1-azabicyclo[2.2.2]octan-3-yloxy]-fluoren-9-oneYield 34%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a 0° C. mixture of 2-hydroxyfluoren-9-one (196 mg, 1.00 mmol; Aldrich), (3R)-quinuclidin-3-ol (151 mg, 1.20 mmol; Acros), and polymer-bound triphenylphosphine (500 mg, 3 mmol/g; Aldrich) in THF (5 mL) was added diethylazodicarboxylate (200 μL, 1.27 mmol; Aldrich). After 1 h, the reaction mixture was allowed to warm to room temperature and was stirred overnight (16 h). The mixture was filtered through diatomaceous earth, the filter pad rinsed with dichloromethane, and the organic extracts purified twice by flash chromatography (80 g silica gel, eluting with 1-5% of 10% NH4OH/MeOH in CH2Cl2) to afford the title compound (104 mg, 0.340 mmol, 34% yield). MS (DCl/NH3): m/z 306 (M+1)+.

Workup

  1. filtrationThe mixture was filtered through diatomaceous earth
  2. washthe filter pad rinsed with dichloromethane
  3. customthe organic extracts purified twice by flash chromatography (80 g silica gel, eluting with 1-5% of 10% NH4OH/MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-9f8de0cb2180498983e881d6910c2e5c
Source dataset
uspto-grants-2008_04
Patent number
US07365193B2

Reaction notes

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