1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → (-)-1-(9-hydroxy-4-methyl-9-trifluoromethyl-9H-fluorene-2-carbonyl)-azetidine-3-carboxylic acid dimethylamide

HRID 1799028Notes

Reaction equation

HRID 1799028 reaction equation
[OH:1][C:2]1([C:19]([F:22])([F:21])[F:20])[C:14]2[CH:13]=[C:12]([C:15]([OH:17])=O)[CH:11]=[C:10]([CH3:18])[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.Cl.[CH3:24][N:25]([CH3:32])[C:26]([CH:28]1[CH2:31][NH:30][CH2:29]1)=[O:27].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1>C(OCC)(=O)C.C(N(CC)CC)C.CN(C)C=O>[CH3:24][N:25]([CH3:32])[C:26]([CH:28]1[CH2:31][N:30]([C:15]([C:12]2[CH:11]=[C:10]([CH3:18])[C:9]3[C:8]4[C:3](=[CH:4][CH:5]=[CH:6][CH:7]=4)[C:2]([OH:1])([C:19]([F:20])([F:21])[F:22])[C:14]=3[CH:13]=2)=[O:17])[CH2:29]1)=[O:27]

Participants

8

Reactant 4

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 53308702N,N-dimethylazetidine-3-carboxamide hydrochlorideHCID 594925279-hydroxy-4-methyl-9-trifluoromethyl-9H-fluorene-2-carboxylic acid

Product 1

HCID 59493074(-)-1-(9-hydroxy-4-methyl-9-trifluoromethyl-9H-fluorene-2-carbonyl)-azetidine-3-carboxylic acid dimethylamideYield 50%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of an optically active form (0.080 g) of 9-hydroxy-4-methyl-9-trifluoromethyl-9H-fluorene-2-carboxylic acid, azetidine-3-carboxylic acid dimethylamide hydrochloride (0.060 g), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.065 g), 1-hydroxybenzotriazole hydrate (0.052 g) and dimethylformamide (2 ml) was added triethylamine (0.073 ml), and the mixture was stirred at room temperature for 3 hr. To the reaction mixture was added ethyl acetate (15 ml), and the mixture was successively washed once with hydrochloric acid, once with water, twice with saturated aqueous sodium hydrogen carbonate and 3 times with water. The organic layer was dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the obtained residue was treated with ethyl ether. This slurry was filtered and the obtained solid was dried to give the title compound (0.054 g, 50%).

Workup

  1. washthe mixture was successively washed once with hydrochloric acid, once with water, twice with saturated aqueous sodium hydrogen carbonate and 3 times with water
  2. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationThe filtrate was concentrated under reduced pressure
  5. additionthe obtained residue was treated with ethyl ether
  6. filtrationThis slurry was filtered
  7. customthe obtained solid was dried

Sources & evidence

ORD record
ord-5d3b91764915403689541f4d44e98de2
Source dataset
uspto-grants-2013_01
Patent number
US08343994B2

Reaction notes

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