1,3-Adamantanedicarboxylic acid → 3-{[4-(2-tert-Butylphenyl)piperazin-1-yl]carbonyl}adamantane-1-carboxylic acid

HRID 534867Notes

Reaction equation

HRID 534867 reaction equation
Cl.Cl.[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]1)([CH3:6])([CH3:5])[CH3:4].[C:19]12([C:32](O)=[O:33])[CH2:28][CH:23]3[CH2:24][CH:25]([CH2:27][C:21]([C:29]([OH:31])=[O:30])([CH2:22]3)[CH2:20]1)[CH2:26]2.Cl.C(N=C=NCCCN(C)C)C.O.ON1C2C=CC=CC=2N=N1>O.CN(C)C=O.C(N(CC)CC)C>[C:3]([C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[N:13]1[CH2:18][CH2:17][N:16]([C:32]([C:19]23[CH2:28][CH:23]4[CH2:24][CH:25]([CH2:27][C:21]([C:29]([OH:31])=[O:30])([CH2:22]4)[CH2:20]2)[CH2:26]3)=[O:33])[CH2:15][CH2:14]1)([CH3:6])([CH3:4])[CH3:5]

Participants

8

Reactant 4

HCID 643391,3-Adamantanedicarboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 667511491-(2-Tert-butylphenyl)piperazine dihydrochloride

Product 1

HCID 667927133-{[4-(2-tert-Butylphenyl)piperazin-1-yl]carbonyl}adamantane-1-carboxylic acidYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

A mixture of 1-(2-tert-butylphenyl)piperazine dihydrochloride obtained in Reference Example 1 (400 mg), 1,3-adamantanedicarboxylic acid (628 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (316 mg), 1-hydroxy-1H-benzotriazole monohydrate (253 mg), triethylamine (0.697 mL), and N,N-dimethylformamide (5 mL) was stirred at room temperature for over-night. Water was added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to purification by high performance liquid chromatography [Column: Gilson, Ltd. High throughput purification system, YMC Combiprep ODS-A, S-5 μm, 50 mm×20 mm; Gradient cycle: H2O (contains 0.1% CF3COOH)-acetonitrile (contains 0.1% CF3COOH), 90:10 (0 min)-90:10 (1 min)-10:90 (4.2 min)-10:90 (5.4 min)-90:10 (5.5 min)-90:10 (5.6 min); Flow rate: 25 mL/min; detection wavelength: UV 220 nm] to give the title compound (352 mg, 61%) as a white solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was subjected to purification by high performance liquid chromatography [Column: Gilson, Ltd. High throughput purification system, YMC Combiprep ODS-A, S-5 μm, 50 mm×20 mm; Gradient cycle: H2O (contains 0.1% CF3COOH)-acetonitrile (contains 0.1% CF3COOH), 90:10 (0 min)-90:10 (1 min)-10:90 (4.2 min)-10:90 (5.4 min)-90:10 (5.5 min)-90:10 (5.6 min); Flow rate: 25 mL/min; detection wavelength: UV 220 nm]

Sources & evidence

ORD record
ord-c73ee78b2135476eb464fac6ae8d5c47
Source dataset
uspto-grants-2014_10
Patent number
US08853215B2

Reaction notes

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