1-Azabicyclo(2.2.2)octane-4-methanol → (Quinuclidin-4-yl)methyl 1H-indole-3-carboxylate

HRID 57324Notes

Reaction equation

HRID 57324 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10](Cl)=[O:11])=[CH:2]1.[N:13]12[CH2:20][CH2:19][C:16]([CH2:21][OH:22])([CH2:17][CH2:18]1)[CH2:15][CH2:14]2>C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([C:10]([O:22][CH2:21][C:16]23[CH2:19][CH2:20][N:13]([CH2:18][CH2:17]2)[CH2:14][CH2:15]3)=[O:11])=[CH:2]1

Participants

4

Reactant 2

HCID 1413111-Azabicyclo(2.2.2)octane-4-methanolHCID 123802781H-Indole-3-carbonyl chloride

Product 1

HCID 25234267(Quinuclidin-4-yl)methyl 1H-indole-3-carboxylateYield 11.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 1H-indole-3-carbonyl chloride (45 mg, 0.25 mmol) in 3 mL of methylene chloride at 0° C. was added (quinuclidin-4-yl)methanol (36 mg, 0.25 mmol) in 2 mL of methylene chloride. The mixture was stirred at room temperature overnight. The solvent was evaporated and water (10 mL) was added. The water layer was basified to pH 12 using 10% aqueous potassium hydroxide and extracted three times with 25 mL each of ethyl acetate. The combined organic layers were dried over sodium sulfate and concentrated to yield 8 mg of desired product. 1HNMR: 12.02 (bs, 1H); 8.13 (d, 1H); 7.9 (m, 1H); 7.42 (m, 1H); 7.18 (m, 2H); 4.3 (bs, 2H); 3.03 (m, 6H); 1.75 (m, 6H). MS (m/e): 285.

Workup

  1. customThe solvent was evaporated
  2. additionwater (10 mL) was added
  3. extractionextracted three times with 25 mL each of ethyl acetate
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7ba8dd39b6834302b642cbe879913a66
Source dataset
uspto-grants-2016_09
Patent number
US09434724B2

Reaction notes

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