Citric Acid → 4-tert-butoxycarbonylamino-N-(4-chlorophenyl)-N-methylbicyclo[2.2.2]octane-1-carboxamide

HRID 228037

Reaction equation

HRID 228037 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]([OH:19])=O)([CH2:13][CH2:14]1)[CH2:11][CH2:10]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].ClC(Cl)(Cl)C#N.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:45][C:46]1[CH:53]=[CH:52][C:49]([NH:50][CH3:51])=[CH:48][CH:47]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>ClCCl.C(N(CC)CC)C>[C:1]([O:5][C:6]([NH:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]([N:50]([C:49]3[CH:52]=[CH:53][C:46]([Cl:45])=[CH:47][CH:48]=3)[CH3:51])=[O:19])([CH2:13][CH2:14]1)[CH2:11][CH2:10]2)=[O:7])([CH3:3])([CH3:2])[CH3:4]

Participants

8

Reactant 5

HCID 311Citric AcidHCID 11011TrichloroacetonitrileHCID 11776TriphenylphosphineHCID 702724-Chloro-N-methylbenzenamineHCID 231507384-{[(Tert-butoxy)carbonyl]amino}bicyclo[2.2.2]octane-1-carboxylic acid

Product 1

HCID 231505174-tert-butoxycarbonylamino-N-(4-chlorophenyl)-N-methylbicyclo[2.2.2]octane-1-carboxamide

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

4-tert-Butoxycarbonylaminobicyclo[2.2.2]octane-1-carboxylic acid (101 mg) was dissolved in dichloromethane (2 mL). To this solution, trichloroacetonitrile (74.0 μL) and triphenylphosphine (196 mg) in dichloromethane (1.5 mL) were sequentially added and the mixture was stirred at room temperature for 2 hours. This was followed by addition of triethylamine (0.18 mL) and 4-chloro-N-methylaniline (98.6 μL) and stirring at room temperature for additional 5.5 hours. The reaction mixture was then poured into aqueous citric acid (5 mL) and was extracted with ethyl acetate (3×10 mL). The ethyl acetate extracts were combined, washed with saturated aqueous sodium bicarbonate solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by a silica gel column (eluant:hexane:ethyl acetate=2:1) to give 4-tert-butoxycarbonylamino-N-(4-chlorophenyl)-N-methylbicyclo[2.2.2]octane-1-carboxamide (91.4 mg) as a white powder.

Workup

  1. stirringstirring at room temperature for additional 5.5 hours
  2. extractionwas extracted with ethyl acetate (3×10 mL)
  3. washwashed with saturated aqueous sodium bicarbonate solution
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by a silica gel column (eluant:hexane:ethyl acetate=2:1)

Sources & evidence

ORD record
ord-3233b079ee80401286c5780430e054a0
Source dataset
uspto-grants-2009_07
Patent number
US07560569B2

Linked notes

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